Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1012A>T (p.Lys338Ter)
Germline
Reviewed by expert panel
Help
Reviewed by expert panel. Learn more about how ClinVar calculates review status.
Pathogenic
for
Breast-ovarian cancer, familial, susceptibility to, 1
Classification is based on the expert panel submission
Sep 2016 by
Evidence-based Network for the Interpretation of Germline M…
Help
The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.1012A>T (p.Lys338Ter)
Variation ID: 54101 Accession: VCV000054101.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43094519 (GRCh38) [ NCBI UCSC ] 17: 41246536 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 24, 2016 Feb 25, 2025 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.1012A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Lys338Ter nonsense NM_001407571.1:c.799A>T NP_001394500.1:p.Lys267Ter nonsense NM_001407581.1:c.1012A>T NP_001394510.1:p.Lys338Ter nonsense NM_001407582.1:c.1012A>T NP_001394511.1:p.Lys338Ter nonsense NM_001407583.1:c.1012A>T NP_001394512.1:p.Lys338Ter nonsense NM_001407585.1:c.1012A>T NP_001394514.1:p.Lys338Ter nonsense NM_001407587.1:c.1009A>T NP_001394516.1:p.Lys337Ter nonsense NM_001407590.1:c.1009A>T NP_001394519.1:p.Lys337Ter nonsense NM_001407591.1:c.1009A>T NP_001394520.1:p.Lys337Ter nonsense NM_001407593.1:c.1012A>T NP_001394522.1:p.Lys338Ter nonsense NM_001407594.1:c.1012A>T NP_001394523.1:p.Lys338Ter nonsense NM_001407596.1:c.1012A>T NP_001394525.1:p.Lys338Ter nonsense NM_001407597.1:c.1012A>T NP_001394526.1:p.Lys338Ter nonsense NM_001407598.1:c.1012A>T NP_001394527.1:p.Lys338Ter nonsense NM_001407602.1:c.1012A>T NP_001394531.1:p.Lys338Ter nonsense NM_001407603.1:c.1012A>T NP_001394532.1:p.Lys338Ter nonsense NM_001407605.1:c.1012A>T NP_001394534.1:p.Lys338Ter nonsense NM_001407610.1:c.1009A>T NP_001394539.1:p.Lys337Ter nonsense NM_001407611.1:c.1009A>T NP_001394540.1:p.Lys337Ter nonsense NM_001407612.1:c.1009A>T NP_001394541.1:p.Lys337Ter nonsense NM_001407613.1:c.1009A>T NP_001394542.1:p.Lys337Ter nonsense NM_001407614.1:c.1009A>T NP_001394543.1:p.Lys337Ter nonsense NM_001407615.1:c.1009A>T NP_001394544.1:p.Lys337Ter nonsense NM_001407616.1:c.1012A>T NP_001394545.1:p.Lys338Ter nonsense NM_001407617.1:c.1012A>T NP_001394546.1:p.Lys338Ter nonsense NM_001407618.1:c.1012A>T NP_001394547.1:p.Lys338Ter nonsense NM_001407619.1:c.1012A>T NP_001394548.1:p.Lys338Ter nonsense NM_001407620.1:c.1012A>T NP_001394549.1:p.Lys338Ter nonsense NM_001407621.1:c.1012A>T NP_001394550.1:p.Lys338Ter nonsense NM_001407622.1:c.1012A>T NP_001394551.1:p.Lys338Ter nonsense NM_001407623.1:c.1012A>T NP_001394552.1:p.Lys338Ter nonsense NM_001407624.1:c.1012A>T NP_001394553.1:p.Lys338Ter nonsense NM_001407625.1:c.1012A>T NP_001394554.1:p.Lys338Ter nonsense NM_001407626.1:c.1012A>T NP_001394555.1:p.Lys338Ter nonsense NM_001407627.1:c.1009A>T NP_001394556.1:p.Lys337Ter nonsense NM_001407628.1:c.1009A>T NP_001394557.1:p.Lys337Ter nonsense NM_001407629.1:c.1009A>T NP_001394558.1:p.Lys337Ter nonsense NM_001407630.1:c.1009A>T NP_001394559.1:p.Lys337Ter nonsense NM_001407631.1:c.1009A>T NP_001394560.1:p.Lys337Ter nonsense NM_001407632.1:c.1009A>T NP_001394561.1:p.Lys337Ter nonsense NM_001407633.1:c.1009A>T NP_001394562.1:p.Lys337Ter nonsense NM_001407634.1:c.1009A>T NP_001394563.1:p.Lys337Ter nonsense NM_001407635.1:c.1009A>T NP_001394564.1:p.Lys337Ter nonsense NM_001407636.1:c.1009A>T NP_001394565.1:p.Lys337Ter nonsense NM_001407637.1:c.1009A>T NP_001394566.1:p.Lys337Ter nonsense NM_001407638.1:c.1009A>T NP_001394567.1:p.Lys337Ter nonsense NM_001407639.1:c.1012A>T NP_001394568.1:p.Lys338Ter nonsense NM_001407640.1:c.1012A>T NP_001394569.1:p.Lys338Ter nonsense NM_001407641.1:c.1012A>T NP_001394570.1:p.Lys338Ter nonsense NM_001407642.1:c.1012A>T NP_001394571.1:p.Lys338Ter nonsense NM_001407644.1:c.1009A>T NP_001394573.1:p.Lys337Ter nonsense NM_001407645.1:c.1009A>T NP_001394574.1:p.Lys337Ter nonsense NM_001407646.1:c.1003A>T NP_001394575.1:p.Lys335Ter nonsense NM_001407647.1:c.1003A>T NP_001394576.1:p.Lys335Ter nonsense NM_001407648.1:c.889A>T NP_001394577.1:p.Lys297Ter nonsense NM_001407649.1:c.886A>T NP_001394578.1:p.Lys296Ter nonsense NM_001407652.1:c.1012A>T NP_001394581.1:p.Lys338Ter nonsense NM_001407653.1:c.934A>T NP_001394582.1:p.Lys312Ter nonsense NM_001407654.1:c.934A>T NP_001394583.1:p.Lys312Ter nonsense NM_001407655.1:c.934A>T NP_001394584.1:p.Lys312Ter nonsense NM_001407656.1:c.934A>T NP_001394585.1:p.Lys312Ter nonsense NM_001407657.1:c.934A>T NP_001394586.1:p.Lys312Ter nonsense NM_001407658.1:c.934A>T NP_001394587.1:p.Lys312Ter nonsense NM_001407659.1:c.931A>T NP_001394588.1:p.Lys311Ter nonsense NM_001407660.1:c.931A>T NP_001394589.1:p.Lys311Ter nonsense NM_001407661.1:c.931A>T NP_001394590.1:p.Lys311Ter nonsense NM_001407662.1:c.931A>T NP_001394591.1:p.Lys311Ter nonsense NM_001407663.1:c.934A>T NP_001394592.1:p.Lys312Ter nonsense NM_001407664.1:c.889A>T NP_001394593.1:p.Lys297Ter nonsense NM_001407665.1:c.889A>T NP_001394594.1:p.Lys297Ter nonsense NM_001407666.1:c.889A>T NP_001394595.1:p.Lys297Ter nonsense NM_001407667.1:c.889A>T NP_001394596.1:p.Lys297Ter nonsense NM_001407668.1:c.889A>T NP_001394597.1:p.Lys297Ter nonsense NM_001407669.1:c.889A>T NP_001394598.1:p.Lys297Ter nonsense NM_001407670.1:c.886A>T NP_001394599.1:p.Lys296Ter nonsense NM_001407671.1:c.886A>T NP_001394600.1:p.Lys296Ter nonsense NM_001407672.1:c.886A>T NP_001394601.1:p.Lys296Ter nonsense NM_001407673.1:c.886A>T NP_001394602.1:p.Lys296Ter nonsense NM_001407674.1:c.889A>T NP_001394603.1:p.Lys297Ter nonsense NM_001407675.1:c.889A>T NP_001394604.1:p.Lys297Ter nonsense NM_001407676.1:c.889A>T NP_001394605.1:p.Lys297Ter nonsense NM_001407677.1:c.889A>T NP_001394606.1:p.Lys297Ter nonsense NM_001407678.1:c.889A>T NP_001394607.1:p.Lys297Ter nonsense NM_001407679.1:c.889A>T NP_001394608.1:p.Lys297Ter nonsense NM_001407680.1:c.889A>T NP_001394609.1:p.Lys297Ter nonsense NM_001407681.1:c.889A>T NP_001394610.1:p.Lys297Ter nonsense NM_001407682.1:c.889A>T NP_001394611.1:p.Lys297Ter nonsense NM_001407683.1:c.889A>T NP_001394612.1:p.Lys297Ter nonsense NM_001407684.1:c.1012A>T NP_001394613.1:p.Lys338Ter nonsense NM_001407685.1:c.886A>T NP_001394614.1:p.Lys296Ter nonsense NM_001407686.1:c.886A>T NP_001394615.1:p.Lys296Ter nonsense NM_001407687.1:c.886A>T NP_001394616.1:p.Lys296Ter nonsense NM_001407688.1:c.886A>T NP_001394617.1:p.Lys296Ter nonsense NM_001407689.1:c.886A>T NP_001394618.1:p.Lys296Ter nonsense NM_001407690.1:c.886A>T NP_001394619.1:p.Lys296Ter nonsense NM_001407691.1:c.886A>T NP_001394620.1:p.Lys296Ter nonsense NM_001407692.1:c.871A>T NP_001394621.1:p.Lys291Ter nonsense NM_001407694.1:c.871A>T NP_001394623.1:p.Lys291Ter nonsense NM_001407695.1:c.871A>T NP_001394624.1:p.Lys291Ter nonsense NM_001407696.1:c.871A>T NP_001394625.1:p.Lys291Ter nonsense NM_001407697.1:c.871A>T NP_001394626.1:p.Lys291Ter nonsense NM_001407698.1:c.871A>T NP_001394627.1:p.Lys291Ter nonsense NM_001407724.1:c.871A>T NP_001394653.1:p.Lys291Ter nonsense NM_001407725.1:c.871A>T NP_001394654.1:p.Lys291Ter nonsense NM_001407726.1:c.871A>T NP_001394655.1:p.Lys291Ter nonsense NM_001407727.1:c.871A>T NP_001394656.1:p.Lys291Ter nonsense NM_001407728.1:c.871A>T NP_001394657.1:p.Lys291Ter nonsense NM_001407729.1:c.871A>T NP_001394658.1:p.Lys291Ter nonsense NM_001407730.1:c.871A>T NP_001394659.1:p.Lys291Ter nonsense NM_001407731.1:c.871A>T NP_001394660.1:p.Lys291Ter nonsense NM_001407732.1:c.871A>T NP_001394661.1:p.Lys291Ter nonsense NM_001407733.1:c.871A>T NP_001394662.1:p.Lys291Ter nonsense NM_001407734.1:c.871A>T NP_001394663.1:p.Lys291Ter nonsense NM_001407735.1:c.871A>T NP_001394664.1:p.Lys291Ter nonsense NM_001407736.1:c.871A>T NP_001394665.1:p.Lys291Ter nonsense NM_001407737.1:c.871A>T NP_001394666.1:p.Lys291Ter nonsense NM_001407738.1:c.871A>T NP_001394667.1:p.Lys291Ter nonsense NM_001407739.1:c.871A>T NP_001394668.1:p.Lys291Ter nonsense NM_001407740.1:c.868A>T NP_001394669.1:p.Lys290Ter nonsense NM_001407741.1:c.868A>T NP_001394670.1:p.Lys290Ter nonsense NM_001407742.1:c.868A>T NP_001394671.1:p.Lys290Ter nonsense NM_001407743.1:c.868A>T NP_001394672.1:p.Lys290Ter nonsense NM_001407744.1:c.868A>T NP_001394673.1:p.Lys290Ter nonsense NM_001407745.1:c.868A>T NP_001394674.1:p.Lys290Ter nonsense NM_001407746.1:c.868A>T NP_001394675.1:p.Lys290Ter nonsense NM_001407747.1:c.868A>T NP_001394676.1:p.Lys290Ter nonsense NM_001407748.1:c.868A>T NP_001394677.1:p.Lys290Ter nonsense NM_001407749.1:c.868A>T NP_001394678.1:p.Lys290Ter nonsense NM_001407750.1:c.871A>T NP_001394679.1:p.Lys291Ter nonsense NM_001407751.1:c.871A>T NP_001394680.1:p.Lys291Ter nonsense NM_001407752.1:c.871A>T NP_001394681.1:p.Lys291Ter nonsense NM_001407838.1:c.868A>T NP_001394767.1:p.Lys290Ter nonsense NM_001407839.1:c.868A>T NP_001394768.1:p.Lys290Ter nonsense NM_001407841.1:c.868A>T NP_001394770.1:p.Lys290Ter nonsense NM_001407842.1:c.868A>T NP_001394771.1:p.Lys290Ter nonsense NM_001407843.1:c.868A>T NP_001394772.1:p.Lys290Ter nonsense NM_001407844.1:c.868A>T NP_001394773.1:p.Lys290Ter nonsense NM_001407845.1:c.868A>T NP_001394774.1:p.Lys290Ter nonsense NM_001407846.1:c.868A>T NP_001394775.1:p.Lys290Ter nonsense NM_001407847.1:c.868A>T NP_001394776.1:p.Lys290Ter nonsense NM_001407848.1:c.868A>T NP_001394777.1:p.Lys290Ter nonsense NM_001407849.1:c.868A>T NP_001394778.1:p.Lys290Ter nonsense NM_001407850.1:c.871A>T NP_001394779.1:p.Lys291Ter nonsense NM_001407851.1:c.871A>T NP_001394780.1:p.Lys291Ter nonsense NM_001407852.1:c.871A>T NP_001394781.1:p.Lys291Ter nonsense NM_001407853.1:c.799A>T NP_001394782.1:p.Lys267Ter nonsense NM_001407854.1:c.1012A>T NP_001394783.1:p.Lys338Ter nonsense NM_001407858.1:c.1012A>T NP_001394787.1:p.Lys338Ter nonsense NM_001407859.1:c.1012A>T NP_001394788.1:p.Lys338Ter nonsense NM_001407860.1:c.1009A>T NP_001394789.1:p.Lys337Ter nonsense NM_001407861.1:c.1009A>T NP_001394790.1:p.Lys337Ter nonsense NM_001407862.1:c.811A>T NP_001394791.1:p.Lys271Ter nonsense NM_001407863.1:c.889A>T NP_001394792.1:p.Lys297Ter nonsense NM_001407874.1:c.808A>T NP_001394803.1:p.Lys270Ter nonsense NM_001407875.1:c.808A>T NP_001394804.1:p.Lys270Ter nonsense NM_001407879.1:c.802A>T NP_001394808.1:p.Lys268Ter nonsense NM_001407881.1:c.802A>T NP_001394810.1:p.Lys268Ter nonsense NM_001407882.1:c.802A>T NP_001394811.1:p.Lys268Ter nonsense NM_001407884.1:c.802A>T NP_001394813.1:p.Lys268Ter nonsense NM_001407885.1:c.802A>T NP_001394814.1:p.Lys268Ter nonsense NM_001407886.1:c.802A>T NP_001394815.1:p.Lys268Ter nonsense NM_001407887.1:c.802A>T NP_001394816.1:p.Lys268Ter nonsense NM_001407889.1:c.802A>T NP_001394818.1:p.Lys268Ter nonsense NM_001407894.1:c.799A>T NP_001394823.1:p.Lys267Ter nonsense NM_001407895.1:c.799A>T NP_001394824.1:p.Lys267Ter nonsense NM_001407896.1:c.799A>T NP_001394825.1:p.Lys267Ter nonsense NM_001407897.1:c.799A>T NP_001394826.1:p.Lys267Ter nonsense NM_001407898.1:c.799A>T NP_001394827.1:p.Lys267Ter nonsense NM_001407899.1:c.799A>T NP_001394828.1:p.Lys267Ter nonsense NM_001407900.1:c.802A>T NP_001394829.1:p.Lys268Ter nonsense NM_001407902.1:c.802A>T NP_001394831.1:p.Lys268Ter nonsense NM_001407904.1:c.802A>T NP_001394833.1:p.Lys268Ter nonsense NM_001407906.1:c.802A>T NP_001394835.1:p.Lys268Ter nonsense NM_001407907.1:c.802A>T NP_001394836.1:p.Lys268Ter nonsense NM_001407908.1:c.802A>T NP_001394837.1:p.Lys268Ter nonsense NM_001407909.1:c.802A>T NP_001394838.1:p.Lys268Ter nonsense NM_001407910.1:c.802A>T NP_001394839.1:p.Lys268Ter nonsense NM_001407915.1:c.799A>T NP_001394844.1:p.Lys267Ter nonsense NM_001407916.1:c.799A>T NP_001394845.1:p.Lys267Ter nonsense NM_001407917.1:c.799A>T NP_001394846.1:p.Lys267Ter nonsense NM_001407918.1:c.799A>T NP_001394847.1:p.Lys267Ter nonsense NM_001407919.1:c.889A>T NP_001394848.1:p.Lys297Ter nonsense NM_001407920.1:c.748A>T NP_001394849.1:p.Lys250Ter nonsense NM_001407921.1:c.748A>T NP_001394850.1:p.Lys250Ter nonsense NM_001407922.1:c.748A>T NP_001394851.1:p.Lys250Ter nonsense NM_001407923.1:c.748A>T NP_001394852.1:p.Lys250Ter nonsense NM_001407924.1:c.748A>T NP_001394853.1:p.Lys250Ter nonsense NM_001407925.1:c.748A>T NP_001394854.1:p.Lys250Ter nonsense NM_001407926.1:c.748A>T NP_001394855.1:p.Lys250Ter nonsense NM_001407927.1:c.748A>T NP_001394856.1:p.Lys250Ter nonsense NM_001407928.1:c.748A>T NP_001394857.1:p.Lys250Ter nonsense NM_001407929.1:c.748A>T NP_001394858.1:p.Lys250Ter nonsense NM_001407930.1:c.745A>T NP_001394859.1:p.Lys249Ter nonsense NM_001407931.1:c.745A>T NP_001394860.1:p.Lys249Ter nonsense NM_001407932.1:c.745A>T NP_001394861.1:p.Lys249Ter nonsense NM_001407933.1:c.748A>T NP_001394862.1:p.Lys250Ter nonsense NM_001407934.1:c.745A>T NP_001394863.1:p.Lys249Ter nonsense NM_001407935.1:c.748A>T NP_001394864.1:p.Lys250Ter nonsense NM_001407936.1:c.745A>T NP_001394865.1:p.Lys249Ter nonsense NM_001407937.1:c.889A>T NP_001394866.1:p.Lys297Ter nonsense NM_001407938.1:c.889A>T NP_001394867.1:p.Lys297Ter nonsense NM_001407939.1:c.889A>T NP_001394868.1:p.Lys297Ter nonsense NM_001407940.1:c.886A>T NP_001394869.1:p.Lys296Ter nonsense NM_001407941.1:c.886A>T NP_001394870.1:p.Lys296Ter nonsense NM_001407942.1:c.871A>T NP_001394871.1:p.Lys291Ter nonsense NM_001407943.1:c.868A>T NP_001394872.1:p.Lys290Ter nonsense NM_001407944.1:c.871A>T NP_001394873.1:p.Lys291Ter nonsense NM_001407945.1:c.871A>T NP_001394874.1:p.Lys291Ter nonsense NM_001407946.1:c.679A>T NP_001394875.1:p.Lys227Ter nonsense NM_001407947.1:c.679A>T NP_001394876.1:p.Lys227Ter nonsense NM_001407948.1:c.679A>T NP_001394877.1:p.Lys227Ter nonsense NM_001407949.1:c.679A>T NP_001394878.1:p.Lys227Ter nonsense NM_001407950.1:c.679A>T NP_001394879.1:p.Lys227Ter nonsense NM_001407951.1:c.679A>T NP_001394880.1:p.Lys227Ter nonsense NM_001407952.1:c.679A>T NP_001394881.1:p.Lys227Ter nonsense NM_001407953.1:c.679A>T NP_001394882.1:p.Lys227Ter nonsense NM_001407954.1:c.676A>T NP_001394883.1:p.Lys226Ter nonsense NM_001407955.1:c.676A>T NP_001394884.1:p.Lys226Ter nonsense NM_001407956.1:c.676A>T NP_001394885.1:p.Lys226Ter nonsense NM_001407957.1:c.679A>T NP_001394886.1:p.Lys227Ter nonsense NM_001407958.1:c.676A>T NP_001394887.1:p.Lys226Ter nonsense NM_001407959.1:c.631A>T NP_001394888.1:p.Lys211Ter nonsense NM_001407960.1:c.631A>T NP_001394889.1:p.Lys211Ter nonsense NM_001407962.1:c.628A>T NP_001394891.1:p.Lys210Ter nonsense NM_001407963.1:c.631A>T NP_001394892.1:p.Lys211Ter nonsense NM_001407964.1:c.868A>T NP_001394893.1:p.Lys290Ter nonsense NM_001407965.1:c.508A>T NP_001394894.1:p.Lys170Ter nonsense NM_001407966.1:c.124A>T NP_001394895.1:p.Lys42Ter nonsense NM_001407967.1:c.124A>T NP_001394896.1:p.Lys42Ter nonsense NM_001407968.1:c.787+225A>T intron variant NM_001407969.1:c.787+225A>T intron variant NM_001407970.1:c.787+225A>T intron variant NM_001407971.1:c.787+225A>T intron variant NM_001407972.1:c.784+225A>T intron variant NM_001407973.1:c.787+225A>T intron variant NM_001407974.1:c.787+225A>T intron variant NM_001407975.1:c.787+225A>T intron variant NM_001407976.1:c.787+225A>T intron variant NM_001407977.1:c.787+225A>T intron variant NM_001407978.1:c.787+225A>T intron variant NM_001407979.1:c.787+225A>T intron variant NM_001407980.1:c.787+225A>T intron variant NM_001407981.1:c.787+225A>T intron variant NM_001407982.1:c.787+225A>T intron variant NM_001407983.1:c.787+225A>T intron variant NM_001407984.1:c.784+225A>T intron variant NM_001407985.1:c.784+225A>T intron variant NM_001407986.1:c.784+225A>T intron variant NM_001407990.1:c.787+225A>T intron variant NM_001407991.1:c.784+225A>T intron variant NM_001407992.1:c.784+225A>T intron variant NM_001407993.1:c.787+225A>T intron variant NM_001408392.1:c.784+225A>T intron variant NM_001408396.1:c.784+225A>T intron variant NM_001408397.1:c.784+225A>T intron variant NM_001408398.1:c.784+225A>T intron variant NM_001408399.1:c.784+225A>T intron variant NM_001408400.1:c.784+225A>T intron variant NM_001408401.1:c.784+225A>T intron variant NM_001408402.1:c.784+225A>T intron variant NM_001408403.1:c.787+225A>T intron variant NM_001408404.1:c.787+225A>T intron variant NM_001408406.1:c.790+222A>T intron variant NM_001408407.1:c.784+225A>T intron variant NM_001408408.1:c.778+225A>T intron variant NM_001408409.1:c.709+225A>T intron variant NM_001408410.1:c.646+225A>T intron variant NM_001408411.1:c.709+225A>T intron variant NM_001408412.1:c.709+225A>T intron variant NM_001408413.1:c.706+225A>T intron variant NM_001408414.1:c.709+225A>T intron variant NM_001408415.1:c.709+225A>T intron variant NM_001408416.1:c.706+225A>T intron variant NM_001408418.1:c.670+1327A>T intron variant NM_001408419.1:c.670+1327A>T intron variant NM_001408420.1:c.670+1327A>T intron variant NM_001408421.1:c.667+1327A>T intron variant NM_001408422.1:c.670+1327A>T intron variant NM_001408423.1:c.670+1327A>T intron variant NM_001408424.1:c.667+1327A>T intron variant NM_001408425.1:c.664+225A>T intron variant NM_001408426.1:c.664+225A>T intron variant NM_001408427.1:c.664+225A>T intron variant NM_001408428.1:c.664+225A>T intron variant NM_001408429.1:c.664+225A>T intron variant NM_001408430.1:c.664+225A>T intron variant NM_001408431.1:c.667+1327A>T intron variant NM_001408432.1:c.661+225A>T intron variant NM_001408433.1:c.661+225A>T intron variant NM_001408434.1:c.661+225A>T intron variant NM_001408435.1:c.661+225A>T intron variant NM_001408436.1:c.664+225A>T intron variant NM_001408437.1:c.664+225A>T intron variant NM_001408438.1:c.664+225A>T intron variant NM_001408439.1:c.664+225A>T intron variant NM_001408440.1:c.664+225A>T intron variant NM_001408441.1:c.664+225A>T intron variant NM_001408442.1:c.664+225A>T intron variant NM_001408443.1:c.664+225A>T intron variant NM_001408444.1:c.664+225A>T intron variant NM_001408445.1:c.661+225A>T intron variant NM_001408446.1:c.661+225A>T intron variant NM_001408447.1:c.661+225A>T intron variant NM_001408448.1:c.661+225A>T intron variant NM_001408450.1:c.661+225A>T intron variant NM_001408451.1:c.652+225A>T intron variant NM_001408452.1:c.646+225A>T intron variant NM_001408453.1:c.646+225A>T intron variant NM_001408454.1:c.646+225A>T intron variant NM_001408455.1:c.646+225A>T intron variant NM_001408456.1:c.646+225A>T intron variant NM_001408457.1:c.646+225A>T intron variant NM_001408458.1:c.646+225A>T intron variant NM_001408459.1:c.646+225A>T intron variant NM_001408460.1:c.646+225A>T intron variant NM_001408461.1:c.646+225A>T intron variant NM_001408462.1:c.643+225A>T intron variant NM_001408463.1:c.643+225A>T intron variant NM_001408464.1:c.643+225A>T intron variant NM_001408465.1:c.643+225A>T intron variant NM_001408466.1:c.646+225A>T intron variant NM_001408467.1:c.646+225A>T intron variant NM_001408468.1:c.643+225A>T intron variant NM_001408469.1:c.646+225A>T intron variant NM_001408470.1:c.643+225A>T intron variant NM_001408472.1:c.787+225A>T intron variant NM_001408473.1:c.784+225A>T intron variant NM_001408474.1:c.586+225A>T intron variant NM_001408475.1:c.583+225A>T intron variant NM_001408476.1:c.586+225A>T intron variant NM_001408478.1:c.577+225A>T intron variant NM_001408479.1:c.577+225A>T intron variant NM_001408480.1:c.577+225A>T intron variant NM_001408481.1:c.577+225A>T intron variant NM_001408482.1:c.577+225A>T intron variant NM_001408483.1:c.577+225A>T intron variant NM_001408484.1:c.577+225A>T intron variant NM_001408485.1:c.577+225A>T intron variant NM_001408489.1:c.577+225A>T intron variant NM_001408490.1:c.574+225A>T intron variant NM_001408491.1:c.574+225A>T intron variant NM_001408492.1:c.577+225A>T intron variant NM_001408493.1:c.574+225A>T intron variant NM_001408494.1:c.548-3487A>T intron variant NM_001408495.1:c.545-3487A>T intron variant NM_001408496.1:c.523+225A>T intron variant NM_001408497.1:c.523+225A>T intron variant NM_001408498.1:c.523+225A>T intron variant NM_001408499.1:c.523+225A>T intron variant NM_001408500.1:c.523+225A>T intron variant NM_001408501.1:c.523+225A>T intron variant NM_001408502.1:c.454+225A>T intron variant NM_001408503.1:c.520+225A>T intron variant NM_001408504.1:c.520+225A>T intron variant NM_001408505.1:c.520+225A>T intron variant NM_001408506.1:c.460+1327A>T intron variant NM_001408507.1:c.460+1327A>T intron variant NM_001408508.1:c.451+225A>T intron variant NM_001408509.1:c.451+225A>T intron variant NM_001408510.1:c.406+225A>T intron variant NM_001408511.1:c.404-3487A>T intron variant NM_001408512.1:c.283+225A>T intron variant NM_001408513.1:c.577+225A>T intron variant NM_001408514.1:c.577+225A>T intron variant NM_007297.4:c.871A>T NP_009228.2:p.Lys291Ter nonsense NM_007298.4:c.787+225A>T intron variant NM_007299.4:c.787+225A>T intron variant NM_007300.4:c.1012A>T NP_009231.2:p.Lys338Ter nonsense NR_027676.1:n.1148A>T NC_000017.11:g.43094519T>A NC_000017.10:g.41246536T>A NG_005905.2:g.123465A>T LRG_292:g.123465A>T LRG_292t1:c.1012A>T LRG_292p1:p.Lys338Ter - Protein change
- K338*, K291*, K210*, K227*, K250*, K297*, K312*, K335*, K211*, K271*, K296*, K42*, K170*, K249*, K311*, K226*, K267*, K268*, K270*, K290*, K337*
- Other names
- -
- Canonical SPDI
- NC_000017.11:43094518:T:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13471 | 15364 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 21, 2022 | RCV000165859.15 | |
| Pathogenic (3) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000241023.13 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Nov 9, 2024 | RCV000496572.17 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 15, 2024 | RCV004998163.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Sep 08, 2016)
C
Contributing to aggregate classification
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000299520.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Mar 29, 2017)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000677718.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
|
|
|
pathogenic
(Jan 15, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV005625996.1
First in ClinVar: Jan 19, 2025 Last updated: Jan 19, 2025 |
Comment:
The BRCA1 c.1012A>T (p.Lys338*) variant causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature in multiple individuals … (more)
The BRCA1 c.1012A>T (p.Lys338*) variant causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature in multiple individuals with breast and/or ovarian cancer (PMIDs: 36169650 (2022), 33654310 (2021), 30972954 (2019), 30078507 (2018), 28176296 (2017)), and observed in screening studies of individuals with BRCA1 and BRCA2 pathogenic variants (PMID: 29446198 (2018), 20127978 (2010), 15998910 (2005)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Nov 09, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001587270.5
First in ClinVar: May 10, 2021 Last updated: Feb 25, 2025 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys338*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Lys338*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 15998910, 28176296, 29446198, 29681614). This variant is also known as 1131A>T. ClinVar contains an entry for this variant (Variation ID: 54101). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Apr 27, 2021)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000682930.2
First in ClinVar: Feb 19, 2018 Last updated: Jan 08, 2022 |
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in at least three individuals affected with breast and ovarian cancer and a suspected hereditary breast cancer family (PMID: 20127978, 29681614, 30972954; Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Oct 02, 2015)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000324927.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Jan 21, 2022)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000216608.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.K338* pathogenic mutation (also known as c.1012A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at … (more)
The p.K338* pathogenic mutation (also known as c.1012A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1012. This changes the amino acid from a lysine to a stop codon within coding exon 9. This alteration has been identified in multiple individuals diagnosed with breast and/or ovarian cancer (Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Copson ER et al. Lancet Oncol, 2018 02;19:169-180; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475; Deng H et al. Mol Genet Genomic Med, 2019 06;7:e672). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Jan 31, 2014)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587092.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
|
|
Comment:
Comment:
The BRCA1 c.1012A>T (p.Lys338*) variant causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature in multiple individuals with breast and/or ovarian cancer (PMIDs: 36169650 (2022), 33654310 (2021), 30972954 (2019), 30078507 (2018), 28176296 (2017)), and observed in screening studies of individuals with BRCA1 and BRCA2 pathogenic variants (PMID: 29446198 (2018), 20127978 (2010), 15998910 (2005)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Lys338*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 15998910, 28176296, 29446198, 29681614). This variant is also known as 1131A>T. ClinVar contains an entry for this variant (Variation ID: 54101). For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in at least three individuals affected with breast and ovarian cancer and a suspected hereditary breast cancer family (PMID: 20127978, 29681614, 30972954; Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The p.K338* pathogenic mutation (also known as c.1012A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1012. This changes the amino acid from a lysine to a stop codon within coding exon 9. This alteration has been identified in multiple individuals diagnosed with breast and/or ovarian cancer (Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Copson ER et al. Lancet Oncol, 2018 02;19:169-180; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475; Deng H et al. Mol Genet Genomic Med, 2019 06;7:e672). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
The BRCA1 c.1012A>T (p.Lys338*) variant causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature in multiple individuals with breast and/or ovarian cancer (PMIDs: 36169650 (2022), 33654310 (2021), 30972954 (2019), 30078507 (2018), 28176296 (2017)), and observed in screening studies of individuals with BRCA1 and BRCA2 pathogenic variants (PMID: 29446198 (2018), 20127978 (2010), 15998910 (2005)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Lys338*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 15998910, 28176296, 29446198, 29681614). This variant is also known as 1131A>T. ClinVar contains an entry for this variant (Variation ID: 54101). For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in at least three individuals affected with breast and ovarian cancer and a suspected hereditary breast cancer family (PMID: 20127978, 29681614, 30972954; Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The p.K338* pathogenic mutation (also known as c.1012A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 1012. This changes the amino acid from a lysine to a stop codon within coding exon 9. This alteration has been identified in multiple individuals diagnosed with breast and/or ovarian cancer (Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Copson ER et al. Lancet Oncol, 2018 02;19:169-180; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475; Deng H et al. Mol Genet Genomic Med, 2019 06;7:e672). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer. | Flaum N | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 36169650 |
| Germline FFPE inherited cancer panel testing in deceased family members: implications for clinical management of unaffected relatives. | Bennett S | European journal of human genetics : EJHG | 2021 | PMID: 33654310 |
| Comprehensive analysis of serum tumor markers and BRCA1/2 germline mutations in Chinese ovarian cancer patients. | Deng H | Molecular genetics & genomic medicine | 2019 | PMID: 30972954 |
| BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
| Prevalence and Spectrum of BRCA1/2 Germline Mutations in Women with Breast Cancer in China Based on Next-Generation Sequencing. | Liang Y | Medical science monitor : international medical journal of experimental and clinical research | 2018 | PMID: 29681614 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. | Copson ER | The Lancet. Oncology | 2018 | PMID: 29337092 |
| BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic-related mutations in BRCA1 associated with an increased risk of ovarian cancer. | Shi T | International journal of cancer | 2017 | PMID: 28176296 |
| Genetic diagnosis of familial breast cancer using clonal sequencing. | Morgan JE | Human mutation | 2010 | PMID: 20127978 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Mutation scanning by meltMADGE: validations using BRCA1 and LDLR, and demonstration of the potential to identify severe, moderate, silent, rare, and paucimorphic mutations in the general population. | Alharbi KK | Genome research | 2005 | PMID: 15998910 |
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Text-mined citations for rs397508826 ...
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Record last updated May 17, 2025
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