Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.188T>A (p.Leu63Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Apr 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.188T>A (p.Leu63Ter)
Variation ID: 54381 Accession: VCV000054381.40
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43106480 (GRCh38) [ NCBI UCSC ] 17: 41258497 (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 Apr 1, 2014 Aug 11, 2024 Apr 22, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.188T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu63Ter nonsense NM_001407571.1:c.-1T>A 5 prime UTR NM_001407581.1:c.188T>A NP_001394510.1:p.Leu63Ter nonsense NM_001407582.1:c.188T>A NP_001394511.1:p.Leu63Ter nonsense NM_001407583.1:c.188T>A NP_001394512.1:p.Leu63Ter nonsense NM_001407585.1:c.188T>A NP_001394514.1:p.Leu63Ter nonsense NM_001407587.1:c.188T>A NP_001394516.1:p.Leu63Ter nonsense NM_001407590.1:c.188T>A NP_001394519.1:p.Leu63Ter nonsense NM_001407591.1:c.188T>A NP_001394520.1:p.Leu63Ter nonsense NM_001407593.1:c.188T>A NP_001394522.1:p.Leu63Ter nonsense NM_001407594.1:c.188T>A NP_001394523.1:p.Leu63Ter nonsense NM_001407596.1:c.188T>A NP_001394525.1:p.Leu63Ter nonsense NM_001407597.1:c.188T>A NP_001394526.1:p.Leu63Ter nonsense NM_001407598.1:c.188T>A NP_001394527.1:p.Leu63Ter nonsense NM_001407602.1:c.188T>A NP_001394531.1:p.Leu63Ter nonsense NM_001407603.1:c.188T>A NP_001394532.1:p.Leu63Ter nonsense NM_001407605.1:c.188T>A NP_001394534.1:p.Leu63Ter nonsense NM_001407610.1:c.188T>A NP_001394539.1:p.Leu63Ter nonsense NM_001407611.1:c.188T>A NP_001394540.1:p.Leu63Ter nonsense NM_001407612.1:c.188T>A NP_001394541.1:p.Leu63Ter nonsense NM_001407613.1:c.188T>A NP_001394542.1:p.Leu63Ter nonsense NM_001407614.1:c.188T>A NP_001394543.1:p.Leu63Ter nonsense NM_001407615.1:c.188T>A NP_001394544.1:p.Leu63Ter nonsense NM_001407616.1:c.188T>A NP_001394545.1:p.Leu63Ter nonsense NM_001407617.1:c.188T>A NP_001394546.1:p.Leu63Ter nonsense NM_001407618.1:c.188T>A NP_001394547.1:p.Leu63Ter nonsense NM_001407619.1:c.188T>A NP_001394548.1:p.Leu63Ter nonsense NM_001407620.1:c.188T>A NP_001394549.1:p.Leu63Ter nonsense NM_001407621.1:c.188T>A NP_001394550.1:p.Leu63Ter nonsense NM_001407622.1:c.188T>A NP_001394551.1:p.Leu63Ter nonsense NM_001407623.1:c.188T>A NP_001394552.1:p.Leu63Ter nonsense NM_001407624.1:c.188T>A NP_001394553.1:p.Leu63Ter nonsense NM_001407625.1:c.188T>A NP_001394554.1:p.Leu63Ter nonsense NM_001407626.1:c.188T>A NP_001394555.1:p.Leu63Ter nonsense NM_001407627.1:c.188T>A NP_001394556.1:p.Leu63Ter nonsense NM_001407628.1:c.188T>A NP_001394557.1:p.Leu63Ter nonsense NM_001407629.1:c.188T>A NP_001394558.1:p.Leu63Ter nonsense NM_001407630.1:c.188T>A NP_001394559.1:p.Leu63Ter nonsense NM_001407631.1:c.188T>A NP_001394560.1:p.Leu63Ter nonsense NM_001407632.1:c.188T>A NP_001394561.1:p.Leu63Ter nonsense NM_001407633.1:c.188T>A NP_001394562.1:p.Leu63Ter nonsense NM_001407634.1:c.188T>A NP_001394563.1:p.Leu63Ter nonsense NM_001407635.1:c.188T>A NP_001394564.1:p.Leu63Ter nonsense NM_001407636.1:c.188T>A NP_001394565.1:p.Leu63Ter nonsense NM_001407637.1:c.188T>A NP_001394566.1:p.Leu63Ter nonsense NM_001407638.1:c.188T>A NP_001394567.1:p.Leu63Ter nonsense NM_001407639.1:c.188T>A NP_001394568.1:p.Leu63Ter nonsense NM_001407640.1:c.188T>A NP_001394569.1:p.Leu63Ter nonsense NM_001407641.1:c.188T>A NP_001394570.1:p.Leu63Ter nonsense NM_001407642.1:c.188T>A NP_001394571.1:p.Leu63Ter nonsense NM_001407644.1:c.188T>A NP_001394573.1:p.Leu63Ter nonsense NM_001407645.1:c.188T>A NP_001394574.1:p.Leu63Ter nonsense NM_001407646.1:c.188T>A NP_001394575.1:p.Leu63Ter nonsense NM_001407647.1:c.188T>A NP_001394576.1:p.Leu63Ter nonsense NM_001407648.1:c.188T>A NP_001394577.1:p.Leu63Ter nonsense NM_001407649.1:c.188T>A NP_001394578.1:p.Leu63Ter nonsense NM_001407652.1:c.188T>A NP_001394581.1:p.Leu63Ter nonsense NM_001407653.1:c.135-1524T>A intron variant NM_001407654.1:c.135-1524T>A intron variant NM_001407655.1:c.135-1524T>A intron variant NM_001407656.1:c.135-1524T>A intron variant NM_001407657.1:c.135-1524T>A intron variant NM_001407658.1:c.135-1524T>A intron variant NM_001407659.1:c.135-1524T>A intron variant NM_001407660.1:c.135-1524T>A intron variant NM_001407661.1:c.135-1524T>A intron variant NM_001407662.1:c.135-1524T>A intron variant NM_001407663.1:c.135-1524T>A intron variant NM_001407664.1:c.188T>A NP_001394593.1:p.Leu63Ter nonsense NM_001407665.1:c.188T>A NP_001394594.1:p.Leu63Ter nonsense NM_001407666.1:c.188T>A NP_001394595.1:p.Leu63Ter nonsense NM_001407667.1:c.188T>A NP_001394596.1:p.Leu63Ter nonsense NM_001407668.1:c.188T>A NP_001394597.1:p.Leu63Ter nonsense NM_001407669.1:c.188T>A NP_001394598.1:p.Leu63Ter nonsense NM_001407670.1:c.188T>A NP_001394599.1:p.Leu63Ter nonsense NM_001407671.1:c.188T>A NP_001394600.1:p.Leu63Ter nonsense NM_001407672.1:c.188T>A NP_001394601.1:p.Leu63Ter nonsense NM_001407673.1:c.188T>A NP_001394602.1:p.Leu63Ter nonsense NM_001407674.1:c.188T>A NP_001394603.1:p.Leu63Ter nonsense NM_001407675.1:c.188T>A NP_001394604.1:p.Leu63Ter nonsense NM_001407676.1:c.188T>A NP_001394605.1:p.Leu63Ter nonsense NM_001407677.1:c.188T>A NP_001394606.1:p.Leu63Ter nonsense NM_001407678.1:c.188T>A NP_001394607.1:p.Leu63Ter nonsense NM_001407679.1:c.188T>A NP_001394608.1:p.Leu63Ter nonsense NM_001407680.1:c.188T>A NP_001394609.1:p.Leu63Ter nonsense NM_001407681.1:c.188T>A NP_001394610.1:p.Leu63Ter nonsense NM_001407682.1:c.188T>A NP_001394611.1:p.Leu63Ter nonsense NM_001407683.1:c.188T>A NP_001394612.1:p.Leu63Ter nonsense NM_001407684.1:c.188T>A NP_001394613.1:p.Leu63Ter nonsense NM_001407685.1:c.188T>A NP_001394614.1:p.Leu63Ter nonsense NM_001407686.1:c.188T>A NP_001394615.1:p.Leu63Ter nonsense NM_001407687.1:c.188T>A NP_001394616.1:p.Leu63Ter nonsense NM_001407688.1:c.188T>A NP_001394617.1:p.Leu63Ter nonsense NM_001407689.1:c.188T>A NP_001394618.1:p.Leu63Ter nonsense NM_001407690.1:c.188T>A NP_001394619.1:p.Leu63Ter nonsense NM_001407691.1:c.188T>A NP_001394620.1:p.Leu63Ter nonsense NM_001407692.1:c.47T>A NP_001394621.1:p.Leu16Ter nonsense NM_001407694.1:c.47T>A NP_001394623.1:p.Leu16Ter nonsense NM_001407695.1:c.47T>A NP_001394624.1:p.Leu16Ter nonsense NM_001407696.1:c.47T>A NP_001394625.1:p.Leu16Ter nonsense NM_001407697.1:c.47T>A NP_001394626.1:p.Leu16Ter nonsense NM_001407698.1:c.47T>A NP_001394627.1:p.Leu16Ter nonsense NM_001407724.1:c.47T>A NP_001394653.1:p.Leu16Ter nonsense NM_001407725.1:c.47T>A NP_001394654.1:p.Leu16Ter nonsense NM_001407726.1:c.47T>A NP_001394655.1:p.Leu16Ter nonsense NM_001407727.1:c.47T>A NP_001394656.1:p.Leu16Ter nonsense NM_001407728.1:c.47T>A NP_001394657.1:p.Leu16Ter nonsense NM_001407729.1:c.47T>A NP_001394658.1:p.Leu16Ter nonsense NM_001407730.1:c.47T>A NP_001394659.1:p.Leu16Ter nonsense NM_001407731.1:c.47T>A NP_001394660.1:p.Leu16Ter nonsense NM_001407732.1:c.47T>A NP_001394661.1:p.Leu16Ter nonsense NM_001407733.1:c.47T>A NP_001394662.1:p.Leu16Ter nonsense NM_001407734.1:c.47T>A NP_001394663.1:p.Leu16Ter nonsense NM_001407735.1:c.47T>A NP_001394664.1:p.Leu16Ter nonsense NM_001407736.1:c.47T>A NP_001394665.1:p.Leu16Ter nonsense NM_001407737.1:c.47T>A NP_001394666.1:p.Leu16Ter nonsense NM_001407738.1:c.47T>A NP_001394667.1:p.Leu16Ter nonsense NM_001407739.1:c.47T>A NP_001394668.1:p.Leu16Ter nonsense NM_001407740.1:c.47T>A NP_001394669.1:p.Leu16Ter nonsense NM_001407741.1:c.47T>A NP_001394670.1:p.Leu16Ter nonsense NM_001407742.1:c.47T>A NP_001394671.1:p.Leu16Ter nonsense NM_001407743.1:c.47T>A NP_001394672.1:p.Leu16Ter nonsense NM_001407744.1:c.47T>A NP_001394673.1:p.Leu16Ter nonsense NM_001407745.1:c.47T>A NP_001394674.1:p.Leu16Ter nonsense NM_001407746.1:c.47T>A NP_001394675.1:p.Leu16Ter nonsense NM_001407747.1:c.47T>A NP_001394676.1:p.Leu16Ter nonsense NM_001407748.1:c.47T>A NP_001394677.1:p.Leu16Ter nonsense NM_001407749.1:c.47T>A NP_001394678.1:p.Leu16Ter nonsense NM_001407750.1:c.47T>A NP_001394679.1:p.Leu16Ter nonsense NM_001407751.1:c.47T>A NP_001394680.1:p.Leu16Ter nonsense NM_001407752.1:c.47T>A NP_001394681.1:p.Leu16Ter nonsense NM_001407838.1:c.47T>A NP_001394767.1:p.Leu16Ter nonsense NM_001407839.1:c.47T>A NP_001394768.1:p.Leu16Ter nonsense NM_001407841.1:c.47T>A NP_001394770.1:p.Leu16Ter nonsense NM_001407842.1:c.47T>A NP_001394771.1:p.Leu16Ter nonsense NM_001407843.1:c.47T>A NP_001394772.1:p.Leu16Ter nonsense NM_001407844.1:c.47T>A NP_001394773.1:p.Leu16Ter nonsense NM_001407845.1:c.47T>A NP_001394774.1:p.Leu16Ter nonsense NM_001407846.1:c.47T>A NP_001394775.1:p.Leu16Ter nonsense NM_001407847.1:c.47T>A NP_001394776.1:p.Leu16Ter nonsense NM_001407848.1:c.47T>A NP_001394777.1:p.Leu16Ter nonsense NM_001407849.1:c.47T>A NP_001394778.1:p.Leu16Ter nonsense NM_001407850.1:c.47T>A NP_001394779.1:p.Leu16Ter nonsense NM_001407851.1:c.47T>A NP_001394780.1:p.Leu16Ter nonsense NM_001407852.1:c.47T>A NP_001394781.1:p.Leu16Ter nonsense NM_001407853.1:c.-1T>A 5 prime UTR NM_001407854.1:c.188T>A NP_001394783.1:p.Leu63Ter nonsense NM_001407858.1:c.188T>A NP_001394787.1:p.Leu63Ter nonsense NM_001407859.1:c.188T>A NP_001394788.1:p.Leu63Ter nonsense NM_001407860.1:c.188T>A NP_001394789.1:p.Leu63Ter nonsense NM_001407861.1:c.188T>A NP_001394790.1:p.Leu63Ter nonsense NM_001407862.1:c.135-1524T>A intron variant NM_001407863.1:c.188T>A NP_001394792.1:p.Leu63Ter nonsense NM_001407874.1:c.135-1524T>A intron variant NM_001407875.1:c.135-1524T>A intron variant NM_001407879.1:c.-1T>A 5 prime UTR NM_001407881.1:c.-1T>A 5 prime UTR NM_001407882.1:c.-1T>A 5 prime UTR NM_001407884.1:c.-1T>A 5 prime UTR NM_001407885.1:c.-1T>A 5 prime UTR NM_001407886.1:c.-1T>A 5 prime UTR NM_001407887.1:c.-1T>A 5 prime UTR NM_001407889.1:c.-1T>A 5 prime UTR NM_001407894.1:c.-1T>A 5 prime UTR NM_001407895.1:c.-1T>A 5 prime UTR NM_001407896.1:c.-1T>A 5 prime UTR NM_001407897.1:c.-1T>A 5 prime UTR NM_001407898.1:c.-1T>A 5 prime UTR NM_001407899.1:c.-1T>A 5 prime UTR NM_001407900.1:c.-1T>A 5 prime UTR NM_001407902.1:c.-1T>A 5 prime UTR NM_001407904.1:c.-1T>A 5 prime UTR NM_001407906.1:c.-1T>A 5 prime UTR NM_001407907.1:c.-1T>A 5 prime UTR NM_001407908.1:c.-1T>A 5 prime UTR NM_001407909.1:c.-1T>A 5 prime UTR NM_001407910.1:c.-1T>A 5 prime UTR NM_001407915.1:c.-1T>A 5 prime UTR NM_001407916.1:c.-1T>A 5 prime UTR NM_001407917.1:c.-1T>A 5 prime UTR NM_001407918.1:c.-1T>A 5 prime UTR NM_001407919.1:c.188T>A NP_001394848.1:p.Leu63Ter nonsense NM_001407920.1:c.47T>A NP_001394849.1:p.Leu16Ter nonsense NM_001407921.1:c.47T>A NP_001394850.1:p.Leu16Ter nonsense NM_001407922.1:c.47T>A NP_001394851.1:p.Leu16Ter nonsense NM_001407923.1:c.47T>A NP_001394852.1:p.Leu16Ter nonsense NM_001407924.1:c.47T>A NP_001394853.1:p.Leu16Ter nonsense NM_001407925.1:c.47T>A NP_001394854.1:p.Leu16Ter nonsense NM_001407926.1:c.47T>A NP_001394855.1:p.Leu16Ter nonsense NM_001407927.1:c.47T>A NP_001394856.1:p.Leu16Ter nonsense NM_001407928.1:c.47T>A NP_001394857.1:p.Leu16Ter nonsense NM_001407929.1:c.47T>A NP_001394858.1:p.Leu16Ter nonsense NM_001407930.1:c.47T>A NP_001394859.1:p.Leu16Ter nonsense NM_001407931.1:c.47T>A NP_001394860.1:p.Leu16Ter nonsense NM_001407932.1:c.47T>A NP_001394861.1:p.Leu16Ter nonsense NM_001407933.1:c.47T>A NP_001394862.1:p.Leu16Ter nonsense NM_001407934.1:c.47T>A NP_001394863.1:p.Leu16Ter nonsense NM_001407935.1:c.47T>A NP_001394864.1:p.Leu16Ter nonsense NM_001407936.1:c.47T>A NP_001394865.1:p.Leu16Ter nonsense NM_001407937.1:c.188T>A NP_001394866.1:p.Leu63Ter nonsense NM_001407938.1:c.188T>A NP_001394867.1:p.Leu63Ter nonsense NM_001407939.1:c.188T>A NP_001394868.1:p.Leu63Ter nonsense NM_001407940.1:c.188T>A NP_001394869.1:p.Leu63Ter nonsense NM_001407941.1:c.188T>A NP_001394870.1:p.Leu63Ter nonsense NM_001407942.1:c.47T>A NP_001394871.1:p.Leu16Ter nonsense NM_001407943.1:c.47T>A NP_001394872.1:p.Leu16Ter nonsense NM_001407944.1:c.47T>A NP_001394873.1:p.Leu16Ter nonsense NM_001407945.1:c.47T>A NP_001394874.1:p.Leu16Ter nonsense NM_001407946.1:c.-1T>A 5 prime UTR NM_001407947.1:c.-1T>A 5 prime UTR NM_001407948.1:c.-1T>A 5 prime UTR NM_001407949.1:c.-1T>A 5 prime UTR NM_001407950.1:c.-1T>A 5 prime UTR NM_001407951.1:c.-1T>A 5 prime UTR NM_001407952.1:c.-1T>A 5 prime UTR NM_001407953.1:c.-1T>A 5 prime UTR NM_001407954.1:c.-1T>A 5 prime UTR NM_001407955.1:c.-1T>A 5 prime UTR NM_001407956.1:c.-1T>A 5 prime UTR NM_001407957.1:c.-1T>A 5 prime UTR NM_001407958.1:c.-1T>A 5 prime UTR NM_001407959.1:c.-169-1524T>A intron variant NM_001407960.1:c.-169-1524T>A intron variant NM_001407962.1:c.-169-1524T>A intron variant NM_001407963.1:c.-169-1524T>A intron variant NM_001407964.1:c.47T>A NP_001394893.1:p.Leu16Ter nonsense NM_001407965.1:c.-169-1524T>A intron variant NM_001407966.1:c.-218-11620T>A intron variant NM_001407967.1:c.-218-11620T>A intron variant NM_001407968.1:c.188T>A NP_001394897.1:p.Leu63Ter nonsense NM_001407969.1:c.188T>A NP_001394898.1:p.Leu63Ter nonsense NM_001407970.1:c.188T>A NP_001394899.1:p.Leu63Ter nonsense NM_001407971.1:c.188T>A NP_001394900.1:p.Leu63Ter nonsense NM_001407972.1:c.188T>A NP_001394901.1:p.Leu63Ter nonsense NM_001407973.1:c.188T>A NP_001394902.1:p.Leu63Ter nonsense NM_001407974.1:c.188T>A NP_001394903.1:p.Leu63Ter nonsense NM_001407975.1:c.188T>A NP_001394904.1:p.Leu63Ter nonsense NM_001407976.1:c.188T>A NP_001394905.1:p.Leu63Ter nonsense NM_001407977.1:c.188T>A NP_001394906.1:p.Leu63Ter nonsense NM_001407978.1:c.188T>A NP_001394907.1:p.Leu63Ter nonsense NM_001407979.1:c.188T>A NP_001394908.1:p.Leu63Ter nonsense NM_001407980.1:c.188T>A NP_001394909.1:p.Leu63Ter nonsense NM_001407981.1:c.188T>A NP_001394910.1:p.Leu63Ter nonsense NM_001407982.1:c.188T>A NP_001394911.1:p.Leu63Ter nonsense NM_001407983.1:c.188T>A NP_001394912.1:p.Leu63Ter nonsense NM_001407984.1:c.188T>A NP_001394913.1:p.Leu63Ter nonsense NM_001407985.1:c.188T>A NP_001394914.1:p.Leu63Ter nonsense NM_001407986.1:c.188T>A NP_001394915.1:p.Leu63Ter nonsense NM_001407990.1:c.188T>A NP_001394919.1:p.Leu63Ter nonsense NM_001407991.1:c.188T>A NP_001394920.1:p.Leu63Ter nonsense NM_001407992.1:c.188T>A NP_001394921.1:p.Leu63Ter nonsense NM_001407993.1:c.188T>A NP_001394922.1:p.Leu63Ter nonsense NM_001408392.1:c.188T>A NP_001395321.1:p.Leu63Ter nonsense NM_001408396.1:c.188T>A NP_001395325.1:p.Leu63Ter nonsense NM_001408397.1:c.188T>A NP_001395326.1:p.Leu63Ter nonsense NM_001408398.1:c.188T>A NP_001395327.1:p.Leu63Ter nonsense NM_001408399.1:c.188T>A NP_001395328.1:p.Leu63Ter nonsense NM_001408400.1:c.188T>A NP_001395329.1:p.Leu63Ter nonsense NM_001408401.1:c.188T>A NP_001395330.1:p.Leu63Ter nonsense NM_001408402.1:c.188T>A NP_001395331.1:p.Leu63Ter nonsense NM_001408403.1:c.188T>A NP_001395332.1:p.Leu63Ter nonsense NM_001408404.1:c.188T>A NP_001395333.1:p.Leu63Ter nonsense NM_001408406.1:c.188T>A NP_001395335.1:p.Leu63Ter nonsense NM_001408407.1:c.188T>A NP_001395336.1:p.Leu63Ter nonsense NM_001408408.1:c.188T>A NP_001395337.1:p.Leu63Ter nonsense NM_001408409.1:c.135-1524T>A intron variant NM_001408410.1:c.47T>A NP_001395339.1:p.Leu16Ter nonsense NM_001408411.1:c.135-1524T>A intron variant NM_001408412.1:c.135-1524T>A intron variant NM_001408413.1:c.135-1524T>A intron variant NM_001408414.1:c.135-1524T>A intron variant NM_001408415.1:c.135-1524T>A intron variant NM_001408416.1:c.135-1524T>A intron variant NM_001408418.1:c.188T>A NP_001395347.1:p.Leu63Ter nonsense NM_001408419.1:c.188T>A NP_001395348.1:p.Leu63Ter nonsense NM_001408420.1:c.188T>A NP_001395349.1:p.Leu63Ter nonsense NM_001408421.1:c.188T>A NP_001395350.1:p.Leu63Ter nonsense NM_001408422.1:c.188T>A NP_001395351.1:p.Leu63Ter nonsense NM_001408423.1:c.188T>A NP_001395352.1:p.Leu63Ter nonsense NM_001408424.1:c.188T>A NP_001395353.1:p.Leu63Ter nonsense NM_001408425.1:c.188T>A NP_001395354.1:p.Leu63Ter nonsense NM_001408426.1:c.188T>A NP_001395355.1:p.Leu63Ter nonsense NM_001408427.1:c.188T>A NP_001395356.1:p.Leu63Ter nonsense NM_001408428.1:c.188T>A NP_001395357.1:p.Leu63Ter nonsense NM_001408429.1:c.188T>A NP_001395358.1:p.Leu63Ter nonsense NM_001408430.1:c.188T>A NP_001395359.1:p.Leu63Ter nonsense NM_001408431.1:c.188T>A NP_001395360.1:p.Leu63Ter nonsense NM_001408432.1:c.188T>A NP_001395361.1:p.Leu63Ter nonsense NM_001408433.1:c.188T>A NP_001395362.1:p.Leu63Ter nonsense NM_001408434.1:c.188T>A NP_001395363.1:p.Leu63Ter nonsense NM_001408435.1:c.188T>A NP_001395364.1:p.Leu63Ter nonsense NM_001408436.1:c.188T>A NP_001395365.1:p.Leu63Ter nonsense NM_001408437.1:c.188T>A NP_001395366.1:p.Leu63Ter nonsense NM_001408438.1:c.188T>A NP_001395367.1:p.Leu63Ter nonsense NM_001408439.1:c.188T>A NP_001395368.1:p.Leu63Ter nonsense NM_001408440.1:c.188T>A NP_001395369.1:p.Leu63Ter nonsense NM_001408441.1:c.188T>A NP_001395370.1:p.Leu63Ter nonsense NM_001408442.1:c.188T>A NP_001395371.1:p.Leu63Ter nonsense NM_001408443.1:c.188T>A NP_001395372.1:p.Leu63Ter nonsense NM_001408444.1:c.188T>A NP_001395373.1:p.Leu63Ter nonsense NM_001408445.1:c.188T>A NP_001395374.1:p.Leu63Ter nonsense NM_001408446.1:c.188T>A NP_001395375.1:p.Leu63Ter nonsense NM_001408447.1:c.188T>A NP_001395376.1:p.Leu63Ter nonsense NM_001408448.1:c.188T>A NP_001395377.1:p.Leu63Ter nonsense NM_001408450.1:c.188T>A NP_001395379.1:p.Leu63Ter nonsense NM_001408451.1:c.81-1524T>A intron variant NM_001408452.1:c.47T>A NP_001395381.1:p.Leu16Ter nonsense NM_001408453.1:c.47T>A NP_001395382.1:p.Leu16Ter nonsense NM_001408454.1:c.47T>A NP_001395383.1:p.Leu16Ter nonsense NM_001408455.1:c.47T>A NP_001395384.1:p.Leu16Ter nonsense NM_001408456.1:c.47T>A NP_001395385.1:p.Leu16Ter nonsense NM_001408457.1:c.47T>A NP_001395386.1:p.Leu16Ter nonsense NM_001408458.1:c.47T>A NP_001395387.1:p.Leu16Ter nonsense NM_001408459.1:c.47T>A NP_001395388.1:p.Leu16Ter nonsense NM_001408460.1:c.47T>A NP_001395389.1:p.Leu16Ter nonsense NM_001408461.1:c.47T>A NP_001395390.1:p.Leu16Ter nonsense NM_001408462.1:c.47T>A NP_001395391.1:p.Leu16Ter nonsense NM_001408463.1:c.47T>A NP_001395392.1:p.Leu16Ter nonsense NM_001408464.1:c.47T>A NP_001395393.1:p.Leu16Ter nonsense NM_001408465.1:c.47T>A NP_001395394.1:p.Leu16Ter nonsense NM_001408466.1:c.47T>A NP_001395395.1:p.Leu16Ter nonsense NM_001408467.1:c.47T>A NP_001395396.1:p.Leu16Ter nonsense NM_001408468.1:c.47T>A NP_001395397.1:p.Leu16Ter nonsense NM_001408469.1:c.47T>A NP_001395398.1:p.Leu16Ter nonsense NM_001408470.1:c.47T>A NP_001395399.1:p.Leu16Ter nonsense NM_001408472.1:c.188T>A NP_001395401.1:p.Leu63Ter nonsense NM_001408473.1:c.188T>A NP_001395402.1:p.Leu63Ter nonsense NM_001408474.1:c.135-1524T>A intron variant NM_001408475.1:c.135-1524T>A intron variant NM_001408476.1:c.135-1524T>A intron variant NM_001408478.1:c.-1T>A 5 prime UTR NM_001408479.1:c.-1T>A 5 prime UTR NM_001408480.1:c.-1T>A 5 prime UTR NM_001408481.1:c.-1T>A 5 prime UTR NM_001408482.1:c.-1T>A 5 prime UTR NM_001408483.1:c.-1T>A 5 prime UTR NM_001408484.1:c.-1T>A 5 prime UTR NM_001408485.1:c.-1T>A 5 prime UTR NM_001408489.1:c.-1T>A 5 prime UTR NM_001408490.1:c.-1T>A 5 prime UTR NM_001408491.1:c.-1T>A 5 prime UTR NM_001408492.1:c.-1T>A 5 prime UTR NM_001408493.1:c.-1T>A 5 prime UTR NM_001408494.1:c.188T>A NP_001395423.1:p.Leu63Ter nonsense NM_001408495.1:c.188T>A NP_001395424.1:p.Leu63Ter nonsense NM_001408496.1:c.47T>A NP_001395425.1:p.Leu16Ter nonsense NM_001408497.1:c.47T>A NP_001395426.1:p.Leu16Ter nonsense NM_001408498.1:c.47T>A NP_001395427.1:p.Leu16Ter nonsense NM_001408499.1:c.47T>A NP_001395428.1:p.Leu16Ter nonsense NM_001408500.1:c.47T>A NP_001395429.1:p.Leu16Ter nonsense NM_001408501.1:c.47T>A NP_001395430.1:p.Leu16Ter nonsense NM_001408502.1:c.-1T>A 5 prime UTR NM_001408503.1:c.47T>A NP_001395432.1:p.Leu16Ter nonsense NM_001408504.1:c.47T>A NP_001395433.1:p.Leu16Ter nonsense NM_001408505.1:c.47T>A NP_001395434.1:p.Leu16Ter nonsense NM_001408506.1:c.-1T>A 5 prime UTR NM_001408507.1:c.-1T>A 5 prime UTR NM_001408508.1:c.-1T>A 5 prime UTR NM_001408509.1:c.-1T>A 5 prime UTR NM_001408510.1:c.-169-1524T>A intron variant NM_001408511.1:c.47T>A NP_001395440.1:p.Leu16Ter nonsense NM_001408512.1:c.-169-1524T>A intron variant NM_001408513.1:c.-1T>A 5 prime UTR NM_001408514.1:c.-1T>A 5 prime UTR NM_007297.4:c.47T>A NP_009228.2:p.Leu16Ter nonsense NM_007298.4:c.188T>A NP_009229.2:p.Leu63Ter nonsense NM_007299.4:c.188T>A NP_009230.2:p.Leu63Ter nonsense NM_007300.4:c.188T>A NP_009231.2:p.Leu63Ter nonsense NM_007304.2:c.188T>A NP_009235.2:p.Leu63Ter nonsense NR_027676.2:n.390T>A NC_000017.11:g.43106480A>T NC_000017.10:g.41258497A>T NG_005905.2:g.111504T>A LRG_292:g.111504T>A LRG_292t1:c.188T>A LRG_292p1:p.Leu63Ter U14680.1:n.307T>A - Protein change
- L63*, L16*
- Other names
-
307T>A
- Canonical SPDI
- NC_000017.11:43106479:A:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
functionally_abnormal; Sequence Ontology [ SO:0002218]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.188T>A, a NONSENSE variant, produced a function score of -2.76, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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.
-
Exome Aggregation Consortium (ExAC) 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 |
13044 | 14850 | |
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 (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 16, 2023 | RCV000047620.24 | |
| Pathogenic (13) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000077499.25 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 22, 2024 | RCV000162847.17 | |
| Pathogenic (1) |
criteria provided, single submitter
|
- | RCV000413802.9 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 11, 2017 | RCV000478996.11 | |
| Pathogenic (1) |
no assertion criteria provided
|
Jul 1, 2021 | RCV003162400.8 |
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
(Apr 22, 2016)
|
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: SCV000282266.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: research
|
Breast Cancer
Affected status: yes
Allele origin:
germline
|
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center
Accession: SCV000492460.1
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
|
|
|
Pathogenic
(Mar 22, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564384.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Feb 14, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000786064.2
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
|
|
|
Pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140643.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
|
Pathogenic
(Oct 08, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial breast-ovarian cancer 1
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001435000.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The c.188T>A (p.Leu63*) variant in the BRCA1 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple patients … (more)
The c.188T>A (p.Leu63*) variant in the BRCA1 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple patients with breast or ovarian cancers (PMID 7627958, 11595708, 19016756, 24249303, 24884479, 26187060). This variant has not been reported in gnomAD. Therefore, the c.188T>A (p.Leu63*) variant in the BRCA1 gene is classified as pathogenic. (less)
|
|
|
Pathogenic
(Sep 29, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000688351.2
First in ClinVar: Feb 19, 2018 Last updated: Jun 19, 2021 |
Comment:
This variant changes 1 nucleotide in exon 4 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 4 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a common cause of breast and/or ovarian cancer in the Japanese population (PMID: 7627958, 24249303, 26187060, 26439132, 29348823). It has also been observed in affected individuals of non-Asian ancestry (PMID: 27741520, 29339979, 29907814). 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
(Jan 21, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600271.2
First in ClinVar: Sep 28, 2017 Last updated: Jan 03, 2022 |
|
|
|
Pathogenic
(Oct 02, 2015)
|
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: SCV000325166.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
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Pathogenic
(Dec 14, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004211776.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
|
Pathogenic
(Mar 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000075633.11
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). It … (more)
This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). It is commonly reported in individuals of Japanese ancestry (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu63*) 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 also known as a common cause of breast and/or ovarian cancer in the Japanese populations (PMID: 24249303, 26187060). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 54381). (less)
|
|
|
Pathogenic
(Mar 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213334.7
First in ClinVar: Mar 24, 2015 Last updated: Aug 11, 2024 |
Comment:
The p.L63* pathogenic mutation (also known as c.188T>A), located in coding exon 3 of the BRCA1 gene, results from a T to A substitution at … (more)
The p.L63* pathogenic mutation (also known as c.188T>A), located in coding exon 3 of the BRCA1 gene, results from a T to A substitution at nucleotide position 188. This changes the amino acid from a leucine to a stop codon within coding exon 3. This mutation has been reported in numerous studies of individuals with personal and/or family history of breast and/or ovarian cancer and is considered a founder mutation in the Japanese population (Inoue R et al. Cancer Res. 1995 Aug; 55(16):3521-4; Sekine M et al. Clin. Cancer Res. 2001 Oct; 7(10):3144-50; Kawahara M et al. J. Hum. Genet., 2004 May;49:391-5; Sugano K et al. Cancer Sci. 2008 Oct;99(10):1967-76; Hirotsu Y et al. Mol Genet Genomic Med, 2015 Mar;3:121-9; Nakamura S et al. Breast Cancer 2015 Sep;22:462-8; Hirasawa A et al. Oncotarget. 2017 Nov 28;8(68):112258-112267; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). Further, a functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this alteration is also designated as 307T>A in published literature. 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
(May 11, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000568435.4
First in ClinVar: Apr 27, 2017 Last updated: Sep 28, 2017 |
Comment:
This variant is denoted BRCA1 c.188T>A at the cDNA level and p.Leu63Ter (L63X) at the protein level. The substitution creates a nonsense variant, which changes … (more)
This variant is denoted BRCA1 c.188T>A at the cDNA level and p.Leu63Ter (L63X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as 307T>A using alternate nomenclature, has been reported in individuals with breast and/or ovarian cancer and is considered a Japanese pathogenic founder variant (Inoue 1995, Sekine 2001, Sugano 2008, Hirotsu 2015, Nakamura 2015). We consider BRCA1 Leu63Ter to be pathogenic. (less)
|
|
|
Pathogenic
(Oct 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916711.1
First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019 |
Comment:
Variant summary: The BRCA1 c.188T>A (p.Leu63X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense … (more)
Variant summary: The BRCA1 c.188T>A (p.Leu63X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant is considered a Japanese founder variant and has been reported in several individuals with personal and family history of HBOC, and was also shown to segregate with the disease (Inoue 1995, Nakamura 2013). This variant is absent in 245910 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Nov 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004823689.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This variant changes 1 nucleotide in exon 4 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 4 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a common cause of breast and/or ovarian cancer in the Japanese population (PMID: 7627958, 24249303, 26187060, 26439132, 29348823). It has also been observed in affected individuals of non-Asian ancestry (PMID: 27741520, 29339979, 29907814). 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)
Number of individuals with the variant: 1
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Pathogenic
(Feb 20, 2004)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144592.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 2
Ethnicity/Population group: Asian
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian, Pacific Islander
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian, Philippine
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Asian
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Pathogenic
(Sep 12, 2011)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000109298.2
First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014 |
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Pathogenic
(Jul 24, 2014)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
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Pathway Genomics
Accession: SCV000189882.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
Comment:
Japanese founder mutation.
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587026.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758505.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Pathogenic
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004244186.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001238037.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.76247796245549
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Comment:
Comment:
The c.188T>A (p.Leu63*) variant in the BRCA1 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple patients with breast or ovarian cancers (PMID 7627958, 11595708, 19016756, 24249303, 24884479, 26187060). This variant has not been reported in gnomAD. Therefore, the c.188T>A (p.Leu63*) variant in the BRCA1 gene is classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 4 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a common cause of breast and/or ovarian cancer in the Japanese population (PMID: 7627958, 24249303, 26187060, 26439132, 29348823). It has also been observed in affected individuals of non-Asian ancestry (PMID: 27741520, 29339979, 29907814). 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:
This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). It is commonly reported in individuals of Japanese ancestry (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu63*) 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 also known as a common cause of breast and/or ovarian cancer in the Japanese populations (PMID: 24249303, 26187060). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 54381).
Comment:
The p.L63* pathogenic mutation (also known as c.188T>A), located in coding exon 3 of the BRCA1 gene, results from a T to A substitution at nucleotide position 188. This changes the amino acid from a leucine to a stop codon within coding exon 3. This mutation has been reported in numerous studies of individuals with personal and/or family history of breast and/or ovarian cancer and is considered a founder mutation in the Japanese population (Inoue R et al. Cancer Res. 1995 Aug; 55(16):3521-4; Sekine M et al. Clin. Cancer Res. 2001 Oct; 7(10):3144-50; Kawahara M et al. J. Hum. Genet., 2004 May;49:391-5; Sugano K et al. Cancer Sci. 2008 Oct;99(10):1967-76; Hirotsu Y et al. Mol Genet Genomic Med, 2015 Mar;3:121-9; Nakamura S et al. Breast Cancer 2015 Sep;22:462-8; Hirasawa A et al. Oncotarget. 2017 Nov 28;8(68):112258-112267; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). Further, a functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this alteration is also designated as 307T>A in published literature. 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.
Comment:
This variant is denoted BRCA1 c.188T>A at the cDNA level and p.Leu63Ter (L63X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as 307T>A using alternate nomenclature, has been reported in individuals with breast and/or ovarian cancer and is considered a Japanese pathogenic founder variant (Inoue 1995, Sekine 2001, Sugano 2008, Hirotsu 2015, Nakamura 2015). We consider BRCA1 Leu63Ter to be pathogenic.
Comment:
Variant summary: The BRCA1 c.188T>A (p.Leu63X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant is considered a Japanese founder variant and has been reported in several individuals with personal and family history of HBOC, and was also shown to segregate with the disease (Inoue 1995, Nakamura 2013). This variant is absent in 245910 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 4 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a common cause of breast and/or ovarian cancer in the Japanese population (PMID: 7627958, 24249303, 26187060, 26439132, 29348823). It has also been observed in affected individuals of non-Asian ancestry (PMID: 27741520, 29339979, 29907814). 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:
Japanese founder mutation.
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001238037.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.188T>A, a NONSENSE variant, produced a function score of -2.76, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.188T>A, a NONSENSE variant, produced a function score of -2.76, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
The c.188T>A (p.Leu63*) variant in the BRCA1 gene is predicted to introduce a premature translation termination codon. This variant has been reported in multiple patients with breast or ovarian cancers (PMID 7627958, 11595708, 19016756, 24249303, 24884479, 26187060). This variant has not been reported in gnomAD. Therefore, the c.188T>A (p.Leu63*) variant in the BRCA1 gene is classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 4 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a common cause of breast and/or ovarian cancer in the Japanese population (PMID: 7627958, 24249303, 26187060, 26439132, 29348823). It has also been observed in affected individuals of non-Asian ancestry (PMID: 27741520, 29339979, 29907814). 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:
This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). It is commonly reported in individuals of Japanese ancestry (PMID: 7627958, 15168169, 19016756, 24249303, 24884479, 25802882, 26187060, 26439132). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu63*) 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 also known as a common cause of breast and/or ovarian cancer in the Japanese populations (PMID: 24249303, 26187060). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 54381).
Comment:
The p.L63* pathogenic mutation (also known as c.188T>A), located in coding exon 3 of the BRCA1 gene, results from a T to A substitution at nucleotide position 188. This changes the amino acid from a leucine to a stop codon within coding exon 3. This mutation has been reported in numerous studies of individuals with personal and/or family history of breast and/or ovarian cancer and is considered a founder mutation in the Japanese population (Inoue R et al. Cancer Res. 1995 Aug; 55(16):3521-4; Sekine M et al. Clin. Cancer Res. 2001 Oct; 7(10):3144-50; Kawahara M et al. J. Hum. Genet., 2004 May;49:391-5; Sugano K et al. Cancer Sci. 2008 Oct;99(10):1967-76; Hirotsu Y et al. Mol Genet Genomic Med, 2015 Mar;3:121-9; Nakamura S et al. Breast Cancer 2015 Sep;22:462-8; Hirasawa A et al. Oncotarget. 2017 Nov 28;8(68):112258-112267; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). Further, a functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Of note, this alteration is also designated as 307T>A in published literature. 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.
Comment:
This variant is denoted BRCA1 c.188T>A at the cDNA level and p.Leu63Ter (L63X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as 307T>A using alternate nomenclature, has been reported in individuals with breast and/or ovarian cancer and is considered a Japanese pathogenic founder variant (Inoue 1995, Sekine 2001, Sugano 2008, Hirotsu 2015, Nakamura 2015). We consider BRCA1 Leu63Ter to be pathogenic.
Comment:
Variant summary: The BRCA1 c.188T>A (p.Leu63X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant is considered a Japanese founder variant and has been reported in several individuals with personal and family history of HBOC, and was also shown to segregate with the disease (Inoue 1995, Nakamura 2013). This variant is absent in 245910 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Comment:
This variant changes 1 nucleotide in exon 4 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant is a common cause of breast and/or ovarian cancer in the Japanese population (PMID: 7627958, 24249303, 26187060, 26439132, 29348823). It has also been observed in affected individuals of non-Asian ancestry (PMID: 27741520, 29339979, 29907814). 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:
Japanese founder mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations. | Wardell CP | Journal of hepatology | 2018 | PMID: 29360550 |
| BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
| Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer. | Hirasawa A | Oncotarget | 2017 | PMID: 29348823 |
| Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry. | Fernandes GC | Oncotarget | 2016 | PMID: 27741520 |
| BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer. | Sakamoto I | Cancer | 2016 | PMID: 26439132 |
| Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries. | Kwong A | Journal of medical genetics | 2016 | PMID: 26187060 |
| Massively Parallel Functional Analysis of BRCA1 RING Domain Variants. | Starita LM | Genetics | 2015 | PMID: 25823446 |
| Detection of BRCA1 and BRCA2 germline mutations in Japanese population using next-generation sequencing. | Hirotsu Y | Molecular genetics & genomic medicine | 2015 | PMID: 25802882 |
| RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
| Prevalence and differentiation of hereditary breast and ovarian cancers in Japan. | Nakamura S | Breast cancer (Tokyo, Japan) | 2015 | PMID: 24249303 |
| Hereditary breast and ovarian cancer: assessment of point mutations and copy number variations in Brazilian patients. | Silva FC | BMC medical genetics | 2014 | PMID: 24884479 |
| A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer. | Karami F | BioMed research international | 2013 | PMID: 24312913 |
| BRCA1 and BRCA2 mutations in the ovarian cancer population across race and ethnicity: special reference to Asia. | Shanmughapriya S | Oncology | 2013 | PMID: 23364291 |
| 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 |
| Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. | Sugano K | Cancer science | 2008 | PMID: 19016756 |
| Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families. | Kawahara M | Journal of human genetics | 2004 | PMID: 15168169 |
| Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population. | Sekine M | Clinical cancer research : an official journal of the American Association for Cancer Research | 2001 | PMID: 11595708 |
| Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases. | Yoshikawa K | Clinical cancer research : an official journal of the American Association for Cancer Research | 1999 | PMID: 10389907 |
| Germline mutation of BRCA1 in Japanese breast cancer families. | Inoue R | Cancer research | 1995 | PMID: 7627958 |
| 12442265, 17591843 | - | - | - | - |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80357086 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.