import { assert } from 'chai' ; import _ from 'lodash' ; import { VariantAnnotation } from 'genome-nexus-ts-api-client' ; import { Mutation } from '../model/Mutation' ; import { annotateMutation , annotateMutations , indexAnnotationsByGenomicLocation , resolveMissingProteinPositions , } from './MutationAnnotator' ; describe ( 'MutationAnnotator' , ( ) => { const variantAnnotations = [ { variant : 'X:g.66937331T>A' , originalVariantQuery : 'X,66937331,66937331,T,A' , colocatedVariants : [ { dbSnpId : 'COSM73703' , } , ] , id : 'X:g.66937331T>A' , assembly_name : 'GRCh37' , seq_region_name : 'X' , start : 66937331 , end : 66937331 , allele_string : 'T/A' , strand : 1 , most_severe_consequence : 'missense_variant' , transcript_consequences : [ { transcript_id : 'ENST00000374690' , hgvsp : 'ENSP00000363822.3:p.Leu729Ile' , hgvsc : 'ENST00000374690.3:c.2185T>A' , variant_allele : 'A' , codons : 'Tta/Ata' , protein_id : 'ENSP00000363822' , protein_start : 729 , protein_end : 729 , gene_symbol : 'AR' , gene_id : 'ENSG00000169083' , amino_acids : 'L/I' , hgnc_id : 644 , canonical : '1' , polyphen_score : 0.999 , polyphen_prediction : 'probably_damaging' , sift_score : 0.01 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_000044.3' ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000396043' , hgvsp : 'ENSP00000379358.2:p.Leu197Ile' , hgvsc : 'ENST00000396043.2:c.589T>A' , variant_allele : 'A' , codons : 'Tta/Ata' , protein_id : 'ENSP00000379358' , protein_start : 197 , protein_end : 197 , gene_symbol : 'AR' , gene_id : 'ENSG00000169083' , amino_acids : 'L/I' , hgnc_id : 644 , polyphen_score : 0.867 , polyphen_prediction : 'possibly_damaging' , sift_score : 0.02 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_001011645.2' ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000396044' , hgvsc : 'ENST00000396044.3:c.2173+5800T>A' , variant_allele : 'A' , protein_id : 'ENSP00000379359' , gene_symbol : 'AR' , gene_id : 'ENSG00000169083' , hgnc_id : 644 , consequence_terms : [ 'intron_variant' ] , } , ] , annotation_summary : { variant : 'X:g.66937331T>A' , genomicLocation : { chromosome : 'X' , start : 66937331 , end : 66937331 , referenceAllele : 'T' , variantAllele : 'A' , } , strandSign : '+' , variantType : 'SNP' , assemblyName : 'GRCh37' , canonicalTranscriptId : 'ENST00000374690' , transcriptConsequences : [ { transcriptId : 'ENST00000374690' , codonChange : 'Tta/Ata' , entrezGeneId : '367' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'AR' , hgvspShort : 'p.L729I' , hgvsp : 'p.Leu729Ile' , hgvsc : 'ENST00000374690.3:c.2185T>A' , proteinPosition : { start : 729 , end : 729 , } , refSeq : 'NM_000044.3' , variantClassification : 'Missense_Mutation' , } , ] , transcriptConsequenceSummaries : [ { transcriptId : 'ENST00000374690' , codonChange : 'Tta/Ata' , entrezGeneId : '367' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'AR' , hgvspShort : 'p.L729I' , hgvsp : 'p.Leu729Ile' , hgvsc : 'ENST00000374690.3:c.2185T>A' , proteinPosition : { start : 729 , end : 729 , } , refSeq : 'NM_000044.3' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000396043' , codonChange : 'Tta/Ata' , entrezGeneId : '367' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'AR' , hgvspShort : 'p.L197I' , hgvsp : 'p.Leu197Ile' , hgvsc : 'ENST00000396043.2:c.589T>A' , proteinPosition : { start : 197 , end : 197 , } , refSeq : 'NM_001011645.2' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000396044' , entrezGeneId : '367' , consequenceTerms : 'intron_variant' , hugoGeneSymbol : 'AR' , hgvspShort : '*725*' , hgvsc : 'ENST00000396044.3:c.2173+5800T>A' , variantClassification : 'Intron' , } , ] , transcriptConsequenceSummary : { transcriptId : 'ENST00000374690' , codonChange : 'Tta/Ata' , entrezGeneId : '367' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'AR' , hgvspShort : 'p.L729I' , hgvsp : 'p.Leu729Ile' , hgvsc : 'ENST00000374690.3:c.2185T>A' , proteinPosition : { start : 729 , end : 729 , } , refSeq : 'NM_000044.3' , variantClassification : 'Missense_Mutation' , } , } , } , { variant : '17:g.41242962_41242963insGA' , originalVariantQuery : '17,41242962,41242963,-,GA' , colocatedVariants : [ { gnomad_nfe_maf : '9.314E-6' , gnomad_nfe_allele : 'A' , gnomad_afr_maf : '0' , gnomad_afr_allele : 'A' , gnomad_eas_maf : '0' , gnomad_eas_allele : 'A' , dbSnpId : 'rs80357742' , } , ] , id : '17:g.41242962_41242963insGA' , assembly_name : 'GRCh37' , seq_region_name : '17' , start : 41242963 , end : 41242962 , allele_string : '-/GA' , strand : 1 , most_severe_consequence : 'frameshift_variant' , transcript_consequences : [ { transcript_id : 'ENST00000309486' , hgvsp : 'ENSP00000310938.4:p.Gln1099LeufsTer11' , hgvsc : 'ENST00000309486.4:c.3294_3295dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000310938' , protein_start : 1099 , protein_end : 1099 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , refseq_transcript_ids : [ 'NM_007297.3' ] , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000346315' , hgvsp : 'ENSP00000246907.4:p.Gln1395LeufsTer11' , hgvsc : 'ENST00000346315.3:c.4182_4183dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000246907' , protein_start : 1395 , protein_end : 1395 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000351666' , hgvsp : 'ENSP00000338007.3:p.Gln212LeufsTer11' , hgvsc : 'ENST00000351666.3:c.633_634dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000338007' , protein_start : 212 , protein_end : 212 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000352993' , hgvsp : 'ENSP00000312236.5:p.Gln253LeufsTer11' , hgvsc : 'ENST00000352993.3:c.756_757dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000312236' , protein_start : 253 , protein_end : 253 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000354071' , hgvsp : 'ENSP00000326002.6:p.Gln1395LeufsTer11' , hgvsc : 'ENST00000354071.3:c.4182_4183dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000326002' , protein_start : 1395 , protein_end : 1395 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000357654' , hgvsp : 'ENSP00000350283.3:p.Gln1395LeufsTer11' , hgvsc : 'ENST00000357654.3:c.4182_4183dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000350283' , protein_start : 1395 , protein_end : 1395 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , canonical : '1' , refseq_transcript_ids : [ 'NM_007294.3' ] , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000412061' , variant_allele : 'GA' , protein_id : 'ENSP00000397145' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000461221' , hgvsc : 'ENST00000461221.1:c.*3965_*3966dup' , variant_allele : 'GA' , protein_id : 'ENSP00000418548' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'splice_region_variant' , '3_prime_UTR_variant' , 'NMD_transcript_variant' , ] , } , { transcript_id : 'ENST00000461574' , hgvsp : 'ENSP00000417241.1:p.Gln160LeufsTer11' , hgvsc : 'ENST00000461574.1:c.476_477dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000417241' , protein_start : 160 , protein_end : 160 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000467274' , variant_allele : 'GA' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000468300' , hgvsp : 'ENSP00000417148.1:p.Gln292LeufsTer11' , hgvsc : 'ENST00000468300.1:c.873_874dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000417148' , protein_start : 292 , protein_end : 292 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , refseq_transcript_ids : [ 'NM_007299.3' ] , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000470026' , variant_allele : 'GA' , protein_id : 'ENSP00000419274' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000471181' , hgvsp : 'ENSP00000418960.2:p.Gln1395LeufsTer11' , hgvsc : 'ENST00000471181.2:c.4182_4183dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000418960' , protein_start : 1395 , protein_end : 1395 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , refseq_transcript_ids : [ 'NM_007300.3' ] , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000473961' , variant_allele : 'GA' , protein_id : 'ENSP00000420201' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000476777' , variant_allele : 'GA' , protein_id : 'ENSP00000417554' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000477152' , variant_allele : 'GA' , protein_id : 'ENSP00000419988' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000478531' , hgvsp : 'ENSP00000420412.1:p.Gln291LeufsTer11' , hgvsc : 'ENST00000478531.1:c.870_871dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000420412' , protein_start : 291 , protein_end : 291 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000484087' , hgvsp : 'ENSP00000419481.1:p.Gln166LeufsTer11' , hgvsc : 'ENST00000484087.1:c.495_496dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000419481' , protein_start : 166 , protein_end : 166 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000487825' , hgvsp : 'ENSP00000418212.1:p.Gln167LeufsTer11' , hgvsc : 'ENST00000487825.1:c.498_499dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000418212' , protein_start : 167 , protein_end : 167 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000491747' , hgvsp : 'ENSP00000420705.2:p.Gln292LeufsTer11' , hgvsc : 'ENST00000491747.2:c.873_874dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000420705' , protein_start : 292 , protein_end : 292 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , refseq_transcript_ids : [ 'NM_007298.3' ] , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000492859' , variant_allele : 'GA' , protein_id : 'ENSP00000420253' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000493795' , hgvsp : 'ENSP00000418775.1:p.Gln1348LeufsTer11' , hgvsc : 'ENST00000493795.1:c.4041_4042dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000418775' , protein_start : 1348 , protein_end : 1348 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000493919' , hgvsp : 'ENSP00000418819.1:p.Gln245LeufsTer11' , hgvsc : 'ENST00000493919.1:c.732_733dup' , variant_allele : 'GA' , codons : 'cag/cTCag' , protein_id : 'ENSP00000418819' , protein_start : 245 , protein_end : 245 , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , amino_acids : 'Q/LX' , hgnc_id : 1100 , consequence_terms : [ 'frameshift_variant' , 'splice_region_variant' , ] , } , { transcript_id : 'ENST00000494123' , variant_allele : 'GA' , protein_id : 'ENSP00000419103' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000497488' , variant_allele : 'GA' , protein_id : 'ENSP00000418986' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000586385' , hgvsc : 'ENST00000586385.1:c.5-26996_5-26995dup' , variant_allele : 'GA' , protein_id : 'ENSP00000465818' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'intron_variant' ] , } , { transcript_id : 'ENST00000591534' , hgvsc : 'ENST00000591534.1:c.-43-16426_-43-16425dup' , variant_allele : 'GA' , protein_id : 'ENSP00000467329' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'intron_variant' ] , } , { transcript_id : 'ENST00000591849' , hgvsc : 'ENST00000591849.1:c.-99+34324_-99+34325dup' , variant_allele : 'GA' , protein_id : 'ENSP00000465347' , gene_symbol : 'BRCA1' , gene_id : 'ENSG00000012048' , hgnc_id : 1100 , consequence_terms : [ 'intron_variant' ] , } , ] , annotation_summary : { variant : '17:g.41242962_41242963insGA' , genomicLocation : { chromosome : '17' , start : 41242962 , end : 41242963 , referenceAllele : '-' , variantAllele : 'GA' , } , strandSign : '+' , variantType : 'INS' , assemblyName : 'GRCh37' , canonicalTranscriptId : 'ENST00000357654' , transcriptConsequences : [ { transcriptId : 'ENST00000357654' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1395Lfs*11' , hgvsp : 'p.Gln1395LeufsTer11' , hgvsc : 'ENST00000357654.3:c.4182_4183dup' , proteinPosition : { start : 1395 , end : 1395 , } , refSeq : 'NM_007294.3' , variantClassification : 'Frame_Shift_Ins' , } , ] , transcriptConsequenceSummaries : [ { transcriptId : 'ENST00000309486' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1099Lfs*11' , hgvsp : 'p.Gln1099LeufsTer11' , hgvsc : 'ENST00000309486.4:c.3294_3295dup' , proteinPosition : { start : 1099 , end : 1099 , } , refSeq : 'NM_007297.3' , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000346315' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1395Lfs*11' , hgvsp : 'p.Gln1395LeufsTer11' , hgvsc : 'ENST00000346315.3:c.4182_4183dup' , proteinPosition : { start : 1395 , end : 1395 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000351666' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q212Lfs*11' , hgvsp : 'p.Gln212LeufsTer11' , hgvsc : 'ENST00000351666.3:c.633_634dup' , proteinPosition : { start : 212 , end : 212 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000352993' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q253Lfs*11' , hgvsp : 'p.Gln253LeufsTer11' , hgvsc : 'ENST00000352993.3:c.756_757dup' , proteinPosition : { start : 253 , end : 253 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000354071' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1395Lfs*11' , hgvsp : 'p.Gln1395LeufsTer11' , hgvsc : 'ENST00000354071.3:c.4182_4183dup' , proteinPosition : { start : 1395 , end : 1395 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000357654' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1395Lfs*11' , hgvsp : 'p.Gln1395LeufsTer11' , hgvsc : 'ENST00000357654.3:c.4182_4183dup' , proteinPosition : { start : 1395 , end : 1395 , } , refSeq : 'NM_007294.3' , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000412061' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000461221' , entrezGeneId : '672' , consequenceTerms : 'splice_region_variant,3_prime_UTR_variant,NMD_transcript_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.X1322_splice' , hgvsc : 'ENST00000461221.1:c.*3965_*3966dup' , proteinPosition : { start : 1322 , end : 1322 , } , variantClassification : 'Splice_Region' , } , { transcriptId : 'ENST00000461574' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q160Lfs*11' , hgvsp : 'p.Gln160LeufsTer11' , hgvsc : 'ENST00000461574.1:c.476_477dup' , proteinPosition : { start : 160 , end : 160 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000467274' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000468300' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q292Lfs*11' , hgvsp : 'p.Gln292LeufsTer11' , hgvsc : 'ENST00000468300.1:c.873_874dup' , proteinPosition : { start : 292 , end : 292 , } , refSeq : 'NM_007299.3' , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000470026' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000471181' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1395Lfs*11' , hgvsp : 'p.Gln1395LeufsTer11' , hgvsc : 'ENST00000471181.2:c.4182_4183dup' , proteinPosition : { start : 1395 , end : 1395 , } , refSeq : 'NM_007300.3' , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000473961' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000476777' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000477152' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000478531' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q291Lfs*11' , hgvsp : 'p.Gln291LeufsTer11' , hgvsc : 'ENST00000478531.1:c.870_871dup' , proteinPosition : { start : 291 , end : 291 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000484087' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q166Lfs*11' , hgvsp : 'p.Gln166LeufsTer11' , hgvsc : 'ENST00000484087.1:c.495_496dup' , proteinPosition : { start : 166 , end : 166 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000487825' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q167Lfs*11' , hgvsp : 'p.Gln167LeufsTer11' , hgvsc : 'ENST00000487825.1:c.498_499dup' , proteinPosition : { start : 167 , end : 167 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000491747' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q292Lfs*11' , hgvsp : 'p.Gln292LeufsTer11' , hgvsc : 'ENST00000491747.2:c.873_874dup' , proteinPosition : { start : 292 , end : 292 , } , refSeq : 'NM_007298.3' , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000492859' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000493795' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1348Lfs*11' , hgvsp : 'p.Gln1348LeufsTer11' , hgvsc : 'ENST00000493795.1:c.4041_4042dup' , proteinPosition : { start : 1348 , end : 1348 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000493919' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q245Lfs*11' , hgvsp : 'p.Gln245LeufsTer11' , hgvsc : 'ENST00000493919.1:c.732_733dup' , proteinPosition : { start : 245 , end : 245 , } , variantClassification : 'Frame_Shift_Ins' , } , { transcriptId : 'ENST00000494123' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000497488' , entrezGeneId : '672' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'BRCA1' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000586385' , entrezGeneId : '672' , consequenceTerms : 'intron_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : '*2*' , hgvsc : 'ENST00000586385.1:c.5-26996_5-26995dup' , variantClassification : 'Intron' , } , { transcriptId : 'ENST00000591534' , entrezGeneId : '672' , consequenceTerms : 'intron_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : '*15*' , hgvsc : 'ENST00000591534.1:c.-43-16426_-43-16425dup' , variantClassification : 'Intron' , } , { transcriptId : 'ENST00000591849' , entrezGeneId : '672' , consequenceTerms : 'intron_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : '*33*' , hgvsc : 'ENST00000591849.1:c.-99+34324_-99+34325dup' , variantClassification : 'Intron' , } , ] , transcriptConsequenceSummary : { transcriptId : 'ENST00000357654' , codonChange : 'cag/cTCag' , entrezGeneId : '672' , consequenceTerms : 'frameshift_variant,splice_region_variant' , hugoGeneSymbol : 'BRCA1' , hgvspShort : 'p.Q1395Lfs*11' , hgvsp : 'p.Gln1395LeufsTer11' , hgvsc : 'ENST00000357654.3:c.4182_4183dup' , proteinPosition : { start : 1395 , end : 1395 , } , refSeq : 'NM_007294.3' , variantClassification : 'Frame_Shift_Ins' , } , } , } , { variant : '13:g.32912813G>T' , originalVariantQuery : '13,32912813,32912813,G,T' , colocatedVariants : [ { dbSnpId : 'COSM946800' , } , { dbSnpId : 'COSM946801' , } , ] , id : '13:g.32912813G>T' , assembly_name : 'GRCh37' , seq_region_name : '13' , start : 32912813 , end : 32912813 , allele_string : 'G/T' , strand : 1 , most_severe_consequence : 'stop_gained' , transcript_consequences : [ { transcript_id : 'ENST00000380152' , hgvsp : 'ENSP00000369497.3:p.Glu1441Ter' , hgvsc : 'ENST00000380152.3:c.4321G>T' , variant_allele : 'T' , codons : 'Gag/Tag' , protein_id : 'ENSP00000369497' , protein_start : 1441 , protein_end : 1441 , gene_symbol : 'BRCA2' , gene_id : 'ENSG00000139618' , amino_acids : 'E/*' , hgnc_id : 1101 , canonical : '1' , consequence_terms : [ 'stop_gained' ] , } , { transcript_id : 'ENST00000544455' , hgvsp : 'ENSP00000439902.1:p.Glu1441Ter' , hgvsc : 'ENST00000544455.1:c.4321G>T' , variant_allele : 'T' , codons : 'Gag/Tag' , protein_id : 'ENSP00000439902' , protein_start : 1441 , protein_end : 1441 , gene_symbol : 'BRCA2' , gene_id : 'ENSG00000139618' , amino_acids : 'E/*' , hgnc_id : 1101 , refseq_transcript_ids : [ 'NM_000059.3' ] , consequence_terms : [ 'stop_gained' ] , } , ] , annotation_summary : { variant : '13:g.32912813G>T' , genomicLocation : { chromosome : '13' , start : 32912813 , end : 32912813 , referenceAllele : 'G' , variantAllele : 'T' , } , strandSign : '+' , variantType : 'SNP' , assemblyName : 'GRCh37' , canonicalTranscriptId : 'ENST00000380152' , transcriptConsequences : [ { transcriptId : 'ENST00000380152' , codonChange : 'Gag/Tag' , entrezGeneId : '675' , consequenceTerms : 'stop_gained' , hugoGeneSymbol : 'BRCA2' , hgvspShort : 'p.E1441*' , hgvsp : 'p.Glu1441Ter' , hgvsc : 'ENST00000380152.3:c.4321G>T' , proteinPosition : { start : 1441 , end : 1441 , } , variantClassification : 'Nonsense_Mutation' , } , ] , transcriptConsequenceSummaries : [ { transcriptId : 'ENST00000380152' , codonChange : 'Gag/Tag' , entrezGeneId : '675' , consequenceTerms : 'stop_gained' , hugoGeneSymbol : 'BRCA2' , hgvspShort : 'p.E1441*' , hgvsp : 'p.Glu1441Ter' , hgvsc : 'ENST00000380152.3:c.4321G>T' , proteinPosition : { start : 1441 , end : 1441 , } , variantClassification : 'Nonsense_Mutation' , } , { transcriptId : 'ENST00000544455' , codonChange : 'Gag/Tag' , entrezGeneId : '675' , consequenceTerms : 'stop_gained' , hugoGeneSymbol : 'BRCA2' , hgvspShort : 'p.E1441*' , hgvsp : 'p.Glu1441Ter' , hgvsc : 'ENST00000544455.1:c.4321G>T' , proteinPosition : { start : 1441 , end : 1441 , } , refSeq : 'NM_000059.3' , variantClassification : 'Nonsense_Mutation' , } , ] , transcriptConsequenceSummary : { transcriptId : 'ENST00000380152' , codonChange : 'Gag/Tag' , entrezGeneId : '675' , consequenceTerms : 'stop_gained' , hugoGeneSymbol : 'BRCA2' , hgvspShort : 'p.E1441*' , hgvsp : 'p.Glu1441Ter' , hgvsc : 'ENST00000380152.3:c.4321G>T' , proteinPosition : { start : 1441 , end : 1441 , } , variantClassification : 'Nonsense_Mutation' , } , } , } , { variant : '12:g.133214671G>C' , originalVariantQuery : '12,133214671,133214671,G,C' , colocatedVariants : [ { dbSnpId : 'COSM78324' , } , ] , id : '12:g.133214671G>C' , assembly_name : 'GRCh37' , seq_region_name : '12' , start : 133214671 , end : 133214671 , allele_string : 'G/C' , strand : 1 , most_severe_consequence : 'missense_variant' , transcript_consequences : [ { transcript_id : 'ENST00000320574' , hgvsp : 'ENSP00000322570.5:p.Asn1869Lys' , hgvsc : 'ENST00000320574.5:c.5607C>G' , variant_allele : 'C' , codons : 'aaC/aaG' , protein_id : 'ENSP00000322570' , protein_start : 1869 , protein_end : 1869 , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , amino_acids : 'N/K' , hgnc_id : 9177 , canonical : '1' , polyphen_score : 0.716 , polyphen_prediction : 'possibly_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_006231.2' ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000416953' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'upstream_gene_variant' ] , } , { transcript_id : 'ENST00000434528' , hgvsc : 'ENST00000434528.3:n.590C>G' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'non_coding_transcript_exon_variant' ] , } , { transcript_id : 'ENST00000441786' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'upstream_gene_variant' ] , } , { transcript_id : 'ENST00000535270' , hgvsp : 'ENSP00000445753.1:p.Asn1842Lys' , hgvsc : 'ENST00000535270.1:c.5526C>G' , variant_allele : 'C' , codons : 'aaC/aaG' , protein_id : 'ENSP00000445753' , protein_start : 1842 , protein_end : 1842 , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , amino_acids : 'N/K' , hgnc_id : 9177 , polyphen_score : 0.408 , polyphen_prediction : 'benign' , sift_score : 0 , sift_prediction : 'deleterious' , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000537064' , hgvsc : 'ENST00000537064.1:c.*5358C>G' , variant_allele : 'C' , protein_id : 'ENSP00000442578' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ '3_prime_UTR_variant' , 'NMD_transcript_variant' , ] , } , { transcript_id : 'ENST00000541213' , hgvsc : 'ENST00000541213.1:n.1085C>G' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'non_coding_transcript_exon_variant' ] , } , { transcript_id : 'ENST00000542362' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000544414' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'upstream_gene_variant' ] , } , { transcript_id : 'ENST00000544692' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'upstream_gene_variant' ] , } , { transcript_id : 'ENST00000544870' , variant_allele : 'C' , gene_symbol : 'POLE' , gene_id : 'ENSG00000177084' , hgnc_id : 9177 , consequence_terms : [ 'upstream_gene_variant' ] , } , ] , annotation_summary : { variant : '12:g.133214671G>C' , genomicLocation : { chromosome : '12' , start : 133214671 , end : 133214671 , referenceAllele : 'G' , variantAllele : 'C' , } , strandSign : '+' , variantType : 'SNP' , assemblyName : 'GRCh37' , canonicalTranscriptId : 'ENST00000320574' , transcriptConsequences : [ { transcriptId : 'ENST00000320574' , codonChange : 'aaC/aaG' , entrezGeneId : '5426' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : 'p.N1869K' , hgvsp : 'p.Asn1869Lys' , hgvsc : 'ENST00000320574.5:c.5607C>G' , proteinPosition : { start : 1869 , end : 1869 , } , refSeq : 'NM_006231.2' , variantClassification : 'Missense_Mutation' , } , ] , transcriptConsequenceSummaries : [ { transcriptId : 'ENST00000320574' , codonChange : 'aaC/aaG' , entrezGeneId : '5426' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : 'p.N1869K' , hgvsp : 'p.Asn1869Lys' , hgvsc : 'ENST00000320574.5:c.5607C>G' , proteinPosition : { start : 1869 , end : 1869 , } , refSeq : 'NM_006231.2' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000416953' , entrezGeneId : '5426' , consequenceTerms : 'upstream_gene_variant' , hugoGeneSymbol : 'POLE' , variantClassification : "5'Flank" , } , { transcriptId : 'ENST00000434528' , entrezGeneId : '5426' , consequenceTerms : 'non_coding_transcript_exon_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : '*197*' , hgvsc : 'ENST00000434528.3:n.590C>G' , variantClassification : 'RNA' , } , { transcriptId : 'ENST00000441786' , entrezGeneId : '5426' , consequenceTerms : 'upstream_gene_variant' , hugoGeneSymbol : 'POLE' , variantClassification : "5'Flank" , } , { transcriptId : 'ENST00000535270' , codonChange : 'aaC/aaG' , entrezGeneId : '5426' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : 'p.N1842K' , hgvsp : 'p.Asn1842Lys' , hgvsc : 'ENST00000535270.1:c.5526C>G' , proteinPosition : { start : 1842 , end : 1842 , } , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000537064' , entrezGeneId : '5426' , consequenceTerms : '3_prime_UTR_variant,NMD_transcript_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : '*1786*' , hgvsc : 'ENST00000537064.1:c.*5358C>G' , variantClassification : "3'UTR" , } , { transcriptId : 'ENST00000541213' , entrezGeneId : '5426' , consequenceTerms : 'non_coding_transcript_exon_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : '*362*' , hgvsc : 'ENST00000541213.1:n.1085C>G' , variantClassification : 'RNA' , } , { transcriptId : 'ENST00000542362' , entrezGeneId : '5426' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'POLE' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000544414' , entrezGeneId : '5426' , consequenceTerms : 'upstream_gene_variant' , hugoGeneSymbol : 'POLE' , variantClassification : "5'Flank" , } , { transcriptId : 'ENST00000544692' , entrezGeneId : '5426' , consequenceTerms : 'upstream_gene_variant' , hugoGeneSymbol : 'POLE' , variantClassification : "5'Flank" , } , { transcriptId : 'ENST00000544870' , entrezGeneId : '5426' , consequenceTerms : 'upstream_gene_variant' , hugoGeneSymbol : 'POLE' , variantClassification : "5'Flank" , } , ] , transcriptConsequenceSummary : { transcriptId : 'ENST00000320574' , codonChange : 'aaC/aaG' , entrezGeneId : '5426' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'POLE' , hgvspShort : 'p.N1869K' , hgvsp : 'p.Asn1869Lys' , hgvsc : 'ENST00000320574.5:c.5607C>G' , proteinPosition : { start : 1869 , end : 1869 , } , refSeq : 'NM_006231.2' , variantClassification : 'Missense_Mutation' , } , } , } , { variant : '17:g.7577539G>A' , originalVariantQuery : '17,7577539,7577539,G,A' , colocatedVariants : [ { dbSnpId : 'CM010465' , } , { dbSnpId : 'CM900211' , } , { dbSnpId : 'COSM10656' , } , { dbSnpId : 'COSM11564' , } , { dbSnpId : 'COSM1189381' , } , { dbSnpId : 'COSM1189382' , } , { dbSnpId : 'COSM1189383' , } , { dbSnpId : 'COSM120005' , } , { dbSnpId : 'COSM120006' , } , { dbSnpId : 'COSM120007' , } , { dbSnpId : 'COSM1640831' , } , { dbSnpId : 'COSM2744594' , } , { dbSnpId : 'COSM3388183' , } , { dbSnpId : 'COSM4271789' , } , { dbSnpId : 'COSM44920' , } , { dbSnpId : 'COSM45116' , } , { dbSnpId : 'rs121912651' , } , { dbSnpId : 'TP53_g.13379C>T' , } , ] , id : '17:g.7577539G>A' , assembly_name : 'GRCh37' , seq_region_name : '17' , start : 7577539 , end : 7577539 , allele_string : 'G/A' , strand : 1 , most_severe_consequence : 'missense_variant' , transcript_consequences : [ { transcript_id : 'ENST00000269305' , hgvsp : 'ENSP00000269305.4:p.Arg248Trp' , hgvsc : 'ENST00000269305.4:c.742C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000269305' , protein_start : 248 , protein_end : 248 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , canonical : '1' , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_001126112.2' , 'NM_001276761.1' , 'NM_001276760.1' , 'NM_000546.5' , 'NM_001126118.1' , ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000359597' , hgvsp : 'ENSP00000352610.4:p.Arg248Trp' , hgvsc : 'ENST00000359597.4:c.742C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000352610' , protein_start : 248 , protein_end : 248 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000413465' , hgvsp : 'ENSP00000410739.2:p.Arg248Trp' , hgvsc : 'ENST00000413465.2:c.742C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000410739' , protein_start : 248 , protein_end : 248 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000420246' , hgvsp : 'ENSP00000391127.2:p.Arg248Trp' , hgvsc : 'ENST00000420246.2:c.742C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000391127' , protein_start : 248 , protein_end : 248 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_001126114.2' , 'NM_001276696.1' ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000445888' , hgvsp : 'ENSP00000391478.2:p.Arg248Trp' , hgvsc : 'ENST00000445888.2:c.742C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000391478' , protein_start : 248 , protein_end : 248 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000455263' , hgvsp : 'ENSP00000398846.2:p.Arg248Trp' , hgvsc : 'ENST00000455263.2:c.742C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000398846' , protein_start : 248 , protein_end : 248 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_001276695.1' , 'NM_001126113.2' ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000503591' , variant_allele : 'A' , protein_id : 'ENSP00000426252' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000504290' , hgvsc : 'ENST00000504290.1:n.624C>T' , variant_allele : 'A' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'non_coding_transcript_exon_variant' , 'non_coding_transcript_variant' , ] , } , { transcript_id : 'ENST00000504937' , hgvsc : 'ENST00000504937.1:n.624C>T' , variant_allele : 'A' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'non_coding_transcript_exon_variant' , 'non_coding_transcript_variant' , ] , } , { transcript_id : 'ENST00000505014' , variant_allele : 'A' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000508793' , variant_allele : 'A' , protein_id : 'ENSP00000424104' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000509690' , hgvsp : 'ENSP00000425104.1:p.Arg116Trp' , hgvsc : 'ENST00000509690.1:c.346C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000425104' , protein_start : 116 , protein_end : 116 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000510385' , hgvsc : 'ENST00000510385.1:n.624C>T' , variant_allele : 'A' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'non_coding_transcript_exon_variant' , 'non_coding_transcript_variant' , ] , } , { transcript_id : 'ENST00000514944' , hgvsp : 'ENSP00000423862.1:p.Arg155Trp' , hgvsc : 'ENST00000514944.1:c.463C>T' , variant_allele : 'A' , codons : 'Cgg/Tgg' , protein_id : 'ENSP00000423862' , protein_start : 155 , protein_end : 155 , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , amino_acids : 'R/W' , hgnc_id : 11998 , polyphen_score : 1 , polyphen_prediction : 'probably_damaging' , sift_score : 0 , sift_prediction : 'deleterious' , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000574684' , variant_allele : 'A' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'downstream_gene_variant' ] , } , { transcript_id : 'ENST00000576024' , variant_allele : 'A' , protein_id : 'ENSP00000458393' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'upstream_gene_variant' ] , } , { transcript_id : 'ENST00000604348' , variant_allele : 'A' , protein_id : 'ENSP00000473895' , gene_symbol : 'TP53' , gene_id : 'ENSG00000141510' , hgnc_id : 11998 , consequence_terms : [ 'downstream_gene_variant' ] , } , ] , annotation_summary : { variant : '17:g.7577539G>A' , genomicLocation : { chromosome : '17' , start : 7577539 , end : 7577539 , referenceAllele : 'G' , variantAllele : 'A' , } , strandSign : '+' , variantType : 'SNP' , assemblyName : 'GRCh37' , canonicalTranscriptId : 'ENST00000269305' , transcriptConsequences : [ { transcriptId : 'ENST00000269305' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000269305.4:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , refSeq : 'NM_001126112.2' , variantClassification : 'Missense_Mutation' , } , ] , transcriptConsequenceSummaries : [ { transcriptId : 'ENST00000269305' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000269305.4:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , refSeq : 'NM_001126112.2' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000359597' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000359597.4:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000413465' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000413465.2:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000420246' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000420246.2:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , refSeq : 'NM_001126114.2' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000445888' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000445888.2:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000455263' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000455263.2:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , refSeq : 'NM_001276695.1' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000503591' , entrezGeneId : '7157' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'TP53' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000504290' , entrezGeneId : '7157' , consequenceTerms : 'non_coding_transcript_exon_variant,non_coding_transcript_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : '*208*' , hgvsc : 'ENST00000504290.1:n.624C>T' , variantClassification : 'RNA' , } , { transcriptId : 'ENST00000504937' , entrezGeneId : '7157' , consequenceTerms : 'non_coding_transcript_exon_variant,non_coding_transcript_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : '*208*' , hgvsc : 'ENST00000504937.1:n.624C>T' , variantClassification : 'RNA' , } , { transcriptId : 'ENST00000505014' , entrezGeneId : '7157' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'TP53' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000508793' , entrezGeneId : '7157' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'TP53' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000509690' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R116W' , hgvsp : 'p.Arg116Trp' , hgvsc : 'ENST00000509690.1:c.346C>T' , proteinPosition : { start : 116 , end : 116 , } , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000510385' , entrezGeneId : '7157' , consequenceTerms : 'non_coding_transcript_exon_variant,non_coding_transcript_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : '*208*' , hgvsc : 'ENST00000510385.1:n.624C>T' , variantClassification : 'RNA' , } , { transcriptId : 'ENST00000514944' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R155W' , hgvsp : 'p.Arg155Trp' , hgvsc : 'ENST00000514944.1:c.463C>T' , proteinPosition : { start : 155 , end : 155 , } , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000574684' , entrezGeneId : '7157' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'TP53' , variantClassification : "3'Flank" , } , { transcriptId : 'ENST00000576024' , entrezGeneId : '7157' , consequenceTerms : 'upstream_gene_variant' , hugoGeneSymbol : 'TP53' , variantClassification : "5'Flank" , } , { transcriptId : 'ENST00000604348' , entrezGeneId : '7157' , consequenceTerms : 'downstream_gene_variant' , hugoGeneSymbol : 'TP53' , variantClassification : "3'Flank" , } , ] , transcriptConsequenceSummary : { transcriptId : 'ENST00000269305' , codonChange : 'Cgg/Tgg' , entrezGeneId : '7157' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'TP53' , hgvspShort : 'p.R248W' , hgvsp : 'p.Arg248Trp' , hgvsc : 'ENST00000269305.4:c.742C>T' , proteinPosition : { start : 248 , end : 248 , } , refSeq : 'NM_001126112.2' , variantClassification : 'Missense_Mutation' , } , } , } , { variant : '10:g.89692905G>A' , originalVariantQuery : '10,89692905,89692905,G,A' , colocatedVariants : [ { dbSnpId : 'CM981670' , } , { dbSnpId : 'CM991081' , } , { dbSnpId : 'COSM5033' , } , { dbSnpId : 'COSM5216' , } , { dbSnpId : 'COSM5277' , } , { dbSnpId : 'COSM5817' , } , { dbSnpId : 'rs121909229' , } , ] , id : '10:g.89692905G>A' , assembly_name : 'GRCh37' , seq_region_name : '10' , start : 89692905 , end : 89692905 , allele_string : 'G/A' , strand : 1 , most_severe_consequence : 'missense_variant' , transcript_consequences : [ { transcript_id : 'ENST00000371953' , hgvsp : 'ENSP00000361021.3:p.Arg130Gln' , hgvsc : 'ENST00000371953.3:c.389G>A' , variant_allele : 'A' , codons : 'cGa/cAa' , protein_id : 'ENSP00000361021' , protein_start : 130 , protein_end : 130 , gene_symbol : 'PTEN' , gene_id : 'ENSG00000171862' , amino_acids : 'R/Q' , hgnc_id : 9588 , canonical : '1' , polyphen_score : 0.989 , polyphen_prediction : 'probably_damaging' , sift_score : 0.02 , sift_prediction : 'deleterious' , refseq_transcript_ids : [ 'NM_000314.4' ] , consequence_terms : [ 'missense_variant' ] , } , { transcript_id : 'ENST00000498703' , hgvsc : 'ENST00000498703.1:n.215G>A' , variant_allele : 'A' , gene_symbol : 'PTEN' , gene_id : 'ENSG00000171862' , hgnc_id : 9588 , consequence_terms : [ 'non_coding_transcript_exon_variant' , 'non_coding_transcript_variant' , ] , } , ] , annotation_summary : { variant : '10:g.89692905G>A' , genomicLocation : { chromosome : '10' , start : 89692905 , end : 89692905 , referenceAllele : 'G' , variantAllele : 'A' , } , strandSign : '+' , variantType : 'SNP' , assemblyName : 'GRCh37' , canonicalTranscriptId : 'ENST00000371953' , transcriptConsequences : [ { transcriptId : 'ENST00000371953' , codonChange : 'cGa/cAa' , entrezGeneId : '5728' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'PTEN' , hgvspShort : 'p.R130Q' , hgvsp : 'p.Arg130Gln' , hgvsc : 'ENST00000371953.3:c.389G>A' , proteinPosition : { start : 130 , end : 130 , } , refSeq : 'NM_000314.4' , variantClassification : 'Missense_Mutation' , } , ] , transcriptConsequenceSummaries : [ { transcriptId : 'ENST00000371953' , codonChange : 'cGa/cAa' , entrezGeneId : '5728' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'PTEN' , hgvspShort : 'p.R130Q' , hgvsp : 'p.Arg130Gln' , hgvsc : 'ENST00000371953.3:c.389G>A' , proteinPosition : { start : 130 , end : 130 , } , refSeq : 'NM_000314.4' , variantClassification : 'Missense_Mutation' , } , { transcriptId : 'ENST00000498703' , entrezGeneId : '5728' , consequenceTerms : 'non_coding_transcript_exon_variant,non_coding_transcript_variant' , hugoGeneSymbol : 'PTEN' , hgvspShort : '*72*' , hgvsc : 'ENST00000498703.1:n.215G>A' , variantClassification : 'RNA' , } , ] , transcriptConsequenceSummary : { transcriptId : 'ENST00000371953' , codonChange : 'cGa/cAa' , entrezGeneId : '5728' , consequenceTerms : 'missense_variant' , hugoGeneSymbol : 'PTEN' , hgvspShort : 'p.R130Q' , hgvsp : 'p.Arg130Gln' , hgvsc : 'ENST00000371953.3:c.389G>A' , proteinPosition : { start : 130 , end : 130 , } , refSeq : 'NM_000314.4' , variantClassification : 'Missense_Mutation' , } , } , } , ] ; let mutationsWithNoGenomicLocation ; let mutationsWithGenomicLocation ; beforeAll ( ( ) => { mutationsWithNoGenomicLocation = [ { gene : { hugoGeneSymbol : 'AR' , } , proteinChange : 'L729I' , mutationType : '' , variantType : '' , } , { gene : { hugoGeneSymbol : 'AR' , } , proteinChange : 'K222N' , mutationType : '' , variantType : '' , } , { gene : { hugoGeneSymbol : 'BRCA1' , } , proteinChange : 'Q1395fs' , mutationType : '' , variantType : '' , } , ] ; mutationsWithGenomicLocation = [ { chromosome : 'X' , startPosition : 66937331 , endPosition : 66937331 , referenceAllele : 'T' , variantAllele : 'A' , } , { chromosome : '17' , startPosition : 41242962 , endPosition : 41242963 , referenceAllele : '-' , variantAllele : 'GA' , } , { chromosome : '13' , startPosition : 32912813 , endPosition : 32912813 , referenceAllele : 'G' , variantAllele : 'T' , } , { chromosome : '12' , startPosition : 133214671 , endPosition : 133214671 , referenceAllele : 'G' , variantAllele : 'C' , } , { chromosome : '17' , startPosition : 7577539 , endPosition : 7577539 , referenceAllele : 'G' , variantAllele : 'A' , } , { chromosome : '10' , startPosition : 89692905 , endPosition : 89692905 , referenceAllele : 'G' , variantAllele : 'A' , } , ] ; } ) ; describe ( 'annotateMutation' , ( ) => { it ( 'should handle failed annotations properly' , ( ) => { const mutation = { chromosome : '6' , startPosition : 29910348 , endPosition : 29910352 , referenceAllele : 'CCGAA' , variantAllele : 'C' , } ; const indexedVariantAnnotations = { '6,29910348,29910352,CCGAA,C' : { originalVariantQuery : '6,29910348,29910352,CCGAA,C' , successfully_annotated : false , variant : '6:g.29910349_29910352del' , } as VariantAnnotation , } ; const annotatedMutation = annotateMutation ( mutation , indexedVariantAnnotations ) ; assert . equal ( annotatedMutation . proteinChange , '' , 'protein change value should be empty due to annotation failure' ) ; } ) ; } ) ; describe ( 'annotateMutations' , ( ) => { it ( "won't annotate mutation data if there are no mutations" , ( ) => { const indexedVariantAnnotations = indexAnnotationsByGenomicLocation ( [ ] ) ; const data = annotateMutations ( [ ] , indexedVariantAnnotations ) ; assert . equal ( data . length , 0 , 'annotated mutation data should be empty' ) ; } ) ; it ( "won't annotate mutation data if there are no mutations with genomic coordinate information" , ( ) => { const indexedVariantAnnotations = indexAnnotationsByGenomicLocation ( [ ] ) ; const data = annotateMutations ( _ . cloneDeep ( mutationsWithNoGenomicLocation ) , indexedVariantAnnotations ) ; assert . deepEqual ( data , mutationsWithNoGenomicLocation , 'annotated mutation data should be identical to the initial input' ) ; } ) ; it ( 'annotates mutation data when the genomic coordinate information is present' , ( ) => { const indexedVariantAnnotations = indexAnnotationsByGenomicLocation ( variantAnnotations as any [ ] ) ; const data = annotateMutations ( mutationsWithGenomicLocation , indexedVariantAnnotations ) ; assert . notDeepEqual ( data , mutationsWithGenomicLocation , 'annotated mutation data should be different than the initial input' ) ; assert . equal ( data [ 0 ] . gene ! . hugoGeneSymbol , 'AR' ) ; assert . isTrue ( data [ 0 ] . proteinChange ! . includes ( 'L729I' ) ) ; assert . isTrue ( data [ 0 ] . mutationType ! . includes ( 'Missense' ) ) ; assert . equal ( data [ 1 ] . gene ! . hugoGeneSymbol , 'BRCA1' ) ; assert . isTrue ( data [ 1 ] . proteinChange ! . includes ( 'Q1395Lfs*11' ) ) ; assert . isTrue ( data [ 1 ] . mutationType ! . includes ( 'Frame_Shift_Ins' ) ) ; assert . equal ( data [ 2 ] . gene ! . hugoGeneSymbol , 'BRCA2' ) ; assert . isTrue ( data [ 2 ] . proteinChange ! . includes ( 'E1441*' ) ) ; assert . isTrue ( data [ 2 ] . mutationType ! . includes ( 'Nonsense' ) ) ; assert . equal ( data [ 3 ] . gene ! . hugoGeneSymbol , 'POLE' ) ; assert . isTrue ( data [ 3 ] . proteinChange ! . includes ( 'N1869K' ) ) ; assert . isTrue ( data [ 3 ] . mutationType ! . includes ( 'Missense' ) ) ; assert . equal ( data [ 4 ] . gene ! . hugoGeneSymbol , 'TP53' ) ; assert . isTrue ( data [ 4 ] . proteinChange ! . includes ( 'R248W' ) ) ; assert . isTrue ( data [ 4 ] . mutationType ! . includes ( 'Missense' ) ) ; assert . equal ( data [ 5 ] . gene ! . hugoGeneSymbol , 'PTEN' ) ; assert . isTrue ( data [ 5 ] . proteinChange ! . includes ( 'R130Q' ) ) ; assert . isTrue ( data [ 5 ] . mutationType ! . includes ( 'Missense' ) ) ; } ) ; } ) ; describe ( 'resolveMissingProteinPositions' , ( ) => { it ( 'resolves missing protein positions from protein change value' , ( ) => { const mutations = [ { proteinChange : 'L729I' , } , { proteinChange : 'K222N' , } , { aminoAcidChange : 'Q1395fs' , } , { proteinChange : 'INVALID' , } , ] ; resolveMissingProteinPositions ( mutations ) ; assert . equal ( mutations [ 0 ] . proteinPosStart , 729 , 'proteinChange = L729I => proteinPosStart = 729' ) ; assert . equal ( mutations [ 1 ] . proteinPosStart , 222 , 'proteinChange = K222N => proteinPosStart = 222' ) ; assert . equal ( mutations [ 2 ] . proteinPosStart , 1395 , 'aminoAcidChange = Q1395fs => proteinPosStart = 1395' ) ; assert . isUndefined ( mutations [ 3 ] . proteinPosStart , 'invalid proteinChange => proteinPosStart = undefined' ) ; } ) ; } ) ; } ) ;