Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4609C>T (p.Gln1537Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 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.4609C>T (p.Gln1537Ter)
Variation ID: 55237 Accession: VCV000055237.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074397 (GRCh38) [ NCBI UCSC ] 17: 41226414 (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 Jun 2, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4609C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln1537Ter nonsense NM_001407571.1:c.4396C>T NP_001394500.1:p.Gln1466Ter nonsense NM_001407581.1:c.4675C>T NP_001394510.1:p.Gln1559Ter nonsense NM_001407582.1:c.4675C>T NP_001394511.1:p.Gln1559Ter nonsense NM_001407583.1:c.4672C>T NP_001394512.1:p.Gln1558Ter nonsense NM_001407585.1:c.4672C>T NP_001394514.1:p.Gln1558Ter nonsense NM_001407587.1:c.4672C>T NP_001394516.1:p.Gln1558Ter nonsense NM_001407590.1:c.4669C>T NP_001394519.1:p.Gln1557Ter nonsense NM_001407591.1:c.4669C>T NP_001394520.1:p.Gln1557Ter nonsense NM_001407593.1:c.4609C>T NP_001394522.1:p.Gln1537Ter nonsense NM_001407594.1:c.4609C>T NP_001394523.1:p.Gln1537Ter nonsense NM_001407596.1:c.4609C>T NP_001394525.1:p.Gln1537Ter nonsense NM_001407597.1:c.4609C>T NP_001394526.1:p.Gln1537Ter nonsense NM_001407598.1:c.4609C>T NP_001394527.1:p.Gln1537Ter nonsense NM_001407602.1:c.4609C>T NP_001394531.1:p.Gln1537Ter nonsense NM_001407603.1:c.4609C>T NP_001394532.1:p.Gln1537Ter nonsense NM_001407605.1:c.4609C>T NP_001394534.1:p.Gln1537Ter nonsense NM_001407610.1:c.4606C>T NP_001394539.1:p.Gln1536Ter nonsense NM_001407611.1:c.4606C>T NP_001394540.1:p.Gln1536Ter nonsense NM_001407612.1:c.4606C>T NP_001394541.1:p.Gln1536Ter nonsense NM_001407613.1:c.4606C>T NP_001394542.1:p.Gln1536Ter nonsense NM_001407614.1:c.4606C>T NP_001394543.1:p.Gln1536Ter nonsense NM_001407615.1:c.4606C>T NP_001394544.1:p.Gln1536Ter nonsense NM_001407616.1:c.4606C>T NP_001394545.1:p.Gln1536Ter nonsense NM_001407617.1:c.4606C>T NP_001394546.1:p.Gln1536Ter nonsense NM_001407618.1:c.4606C>T NP_001394547.1:p.Gln1536Ter nonsense NM_001407619.1:c.4606C>T NP_001394548.1:p.Gln1536Ter nonsense NM_001407620.1:c.4606C>T NP_001394549.1:p.Gln1536Ter nonsense NM_001407621.1:c.4606C>T NP_001394550.1:p.Gln1536Ter nonsense NM_001407622.1:c.4606C>T NP_001394551.1:p.Gln1536Ter nonsense NM_001407623.1:c.4606C>T NP_001394552.1:p.Gln1536Ter nonsense NM_001407624.1:c.4606C>T NP_001394553.1:p.Gln1536Ter nonsense NM_001407625.1:c.4606C>T NP_001394554.1:p.Gln1536Ter nonsense NM_001407626.1:c.4606C>T NP_001394555.1:p.Gln1536Ter nonsense NM_001407627.1:c.4603C>T NP_001394556.1:p.Gln1535Ter nonsense NM_001407628.1:c.4603C>T NP_001394557.1:p.Gln1535Ter nonsense NM_001407629.1:c.4603C>T NP_001394558.1:p.Gln1535Ter nonsense NM_001407630.1:c.4603C>T NP_001394559.1:p.Gln1535Ter nonsense NM_001407631.1:c.4603C>T NP_001394560.1:p.Gln1535Ter nonsense NM_001407632.1:c.4603C>T NP_001394561.1:p.Gln1535Ter nonsense NM_001407633.1:c.4603C>T NP_001394562.1:p.Gln1535Ter nonsense NM_001407634.1:c.4603C>T NP_001394563.1:p.Gln1535Ter nonsense NM_001407635.1:c.4603C>T NP_001394564.1:p.Gln1535Ter nonsense NM_001407636.1:c.4603C>T NP_001394565.1:p.Gln1535Ter nonsense NM_001407637.1:c.4603C>T NP_001394566.1:p.Gln1535Ter nonsense NM_001407638.1:c.4603C>T NP_001394567.1:p.Gln1535Ter nonsense NM_001407639.1:c.4603C>T NP_001394568.1:p.Gln1535Ter nonsense NM_001407640.1:c.4603C>T NP_001394569.1:p.Gln1535Ter nonsense NM_001407641.1:c.4603C>T NP_001394570.1:p.Gln1535Ter nonsense NM_001407642.1:c.4603C>T NP_001394571.1:p.Gln1535Ter nonsense NM_001407644.1:c.4600C>T NP_001394573.1:p.Gln1534Ter nonsense NM_001407645.1:c.4600C>T NP_001394574.1:p.Gln1534Ter nonsense NM_001407646.1:c.4597C>T NP_001394575.1:p.Gln1533Ter nonsense NM_001407647.1:c.4594C>T NP_001394576.1:p.Gln1532Ter nonsense NM_001407648.1:c.4552C>T NP_001394577.1:p.Gln1518Ter nonsense NM_001407649.1:c.4549C>T NP_001394578.1:p.Gln1517Ter nonsense NM_001407652.1:c.4609C>T NP_001394581.1:p.Gln1537Ter nonsense NM_001407653.1:c.4531C>T NP_001394582.1:p.Gln1511Ter nonsense NM_001407654.1:c.4531C>T NP_001394583.1:p.Gln1511Ter nonsense NM_001407655.1:c.4531C>T NP_001394584.1:p.Gln1511Ter nonsense NM_001407656.1:c.4528C>T NP_001394585.1:p.Gln1510Ter nonsense NM_001407657.1:c.4528C>T NP_001394586.1:p.Gln1510Ter nonsense NM_001407658.1:c.4528C>T NP_001394587.1:p.Gln1510Ter nonsense NM_001407659.1:c.4525C>T NP_001394588.1:p.Gln1509Ter nonsense NM_001407660.1:c.4525C>T NP_001394589.1:p.Gln1509Ter nonsense NM_001407661.1:c.4525C>T NP_001394590.1:p.Gln1509Ter nonsense NM_001407662.1:c.4525C>T NP_001394591.1:p.Gln1509Ter nonsense NM_001407663.1:c.4525C>T NP_001394592.1:p.Gln1509Ter nonsense NM_001407664.1:c.4486C>T NP_001394593.1:p.Gln1496Ter nonsense NM_001407665.1:c.4486C>T NP_001394594.1:p.Gln1496Ter nonsense NM_001407666.1:c.4486C>T NP_001394595.1:p.Gln1496Ter nonsense NM_001407667.1:c.4486C>T NP_001394596.1:p.Gln1496Ter nonsense NM_001407668.1:c.4486C>T NP_001394597.1:p.Gln1496Ter nonsense NM_001407669.1:c.4486C>T NP_001394598.1:p.Gln1496Ter nonsense NM_001407670.1:c.4483C>T NP_001394599.1:p.Gln1495Ter nonsense NM_001407671.1:c.4483C>T NP_001394600.1:p.Gln1495Ter nonsense NM_001407672.1:c.4483C>T NP_001394601.1:p.Gln1495Ter nonsense NM_001407673.1:c.4483C>T NP_001394602.1:p.Gln1495Ter nonsense NM_001407674.1:c.4483C>T NP_001394603.1:p.Gln1495Ter nonsense NM_001407675.1:c.4483C>T NP_001394604.1:p.Gln1495Ter nonsense NM_001407676.1:c.4483C>T NP_001394605.1:p.Gln1495Ter nonsense NM_001407677.1:c.4483C>T NP_001394606.1:p.Gln1495Ter nonsense NM_001407678.1:c.4483C>T NP_001394607.1:p.Gln1495Ter nonsense NM_001407679.1:c.4483C>T NP_001394608.1:p.Gln1495Ter nonsense NM_001407680.1:c.4483C>T NP_001394609.1:p.Gln1495Ter nonsense NM_001407681.1:c.4480C>T NP_001394610.1:p.Gln1494Ter nonsense NM_001407682.1:c.4480C>T NP_001394611.1:p.Gln1494Ter nonsense NM_001407683.1:c.4480C>T NP_001394612.1:p.Gln1494Ter nonsense NM_001407684.1:c.4609C>T NP_001394613.1:p.Gln1537Ter nonsense NM_001407685.1:c.4480C>T NP_001394614.1:p.Gln1494Ter nonsense NM_001407686.1:c.4480C>T NP_001394615.1:p.Gln1494Ter nonsense NM_001407687.1:c.4480C>T NP_001394616.1:p.Gln1494Ter nonsense NM_001407688.1:c.4480C>T NP_001394617.1:p.Gln1494Ter nonsense NM_001407689.1:c.4480C>T NP_001394618.1:p.Gln1494Ter nonsense NM_001407690.1:c.4477C>T NP_001394619.1:p.Gln1493Ter nonsense NM_001407691.1:c.4477C>T NP_001394620.1:p.Gln1493Ter nonsense NM_001407692.1:c.4468C>T NP_001394621.1:p.Gln1490Ter nonsense NM_001407694.1:c.4468C>T NP_001394623.1:p.Gln1490Ter nonsense NM_001407695.1:c.4468C>T NP_001394624.1:p.Gln1490Ter nonsense NM_001407696.1:c.4468C>T NP_001394625.1:p.Gln1490Ter nonsense NM_001407697.1:c.4468C>T NP_001394626.1:p.Gln1490Ter nonsense NM_001407698.1:c.4468C>T NP_001394627.1:p.Gln1490Ter nonsense NM_001407724.1:c.4468C>T NP_001394653.1:p.Gln1490Ter nonsense NM_001407725.1:c.4468C>T NP_001394654.1:p.Gln1490Ter nonsense NM_001407726.1:c.4468C>T NP_001394655.1:p.Gln1490Ter nonsense NM_001407727.1:c.4468C>T NP_001394656.1:p.Gln1490Ter nonsense NM_001407728.1:c.4468C>T NP_001394657.1:p.Gln1490Ter nonsense NM_001407729.1:c.4468C>T NP_001394658.1:p.Gln1490Ter nonsense NM_001407730.1:c.4468C>T NP_001394659.1:p.Gln1490Ter nonsense NM_001407731.1:c.4468C>T NP_001394660.1:p.Gln1490Ter nonsense NM_001407732.1:c.4465C>T NP_001394661.1:p.Gln1489Ter nonsense NM_001407733.1:c.4465C>T NP_001394662.1:p.Gln1489Ter nonsense NM_001407734.1:c.4465C>T NP_001394663.1:p.Gln1489Ter nonsense NM_001407735.1:c.4465C>T NP_001394664.1:p.Gln1489Ter nonsense NM_001407736.1:c.4465C>T NP_001394665.1:p.Gln1489Ter nonsense NM_001407737.1:c.4465C>T NP_001394666.1:p.Gln1489Ter nonsense NM_001407738.1:c.4465C>T NP_001394667.1:p.Gln1489Ter nonsense NM_001407739.1:c.4465C>T NP_001394668.1:p.Gln1489Ter nonsense NM_001407740.1:c.4465C>T NP_001394669.1:p.Gln1489Ter nonsense NM_001407741.1:c.4465C>T NP_001394670.1:p.Gln1489Ter nonsense NM_001407742.1:c.4465C>T NP_001394671.1:p.Gln1489Ter nonsense NM_001407743.1:c.4465C>T NP_001394672.1:p.Gln1489Ter nonsense NM_001407744.1:c.4465C>T NP_001394673.1:p.Gln1489Ter nonsense NM_001407745.1:c.4465C>T NP_001394674.1:p.Gln1489Ter nonsense NM_001407746.1:c.4465C>T NP_001394675.1:p.Gln1489Ter nonsense NM_001407747.1:c.4465C>T NP_001394676.1:p.Gln1489Ter nonsense NM_001407748.1:c.4465C>T NP_001394677.1:p.Gln1489Ter nonsense NM_001407749.1:c.4465C>T NP_001394678.1:p.Gln1489Ter nonsense NM_001407750.1:c.4465C>T NP_001394679.1:p.Gln1489Ter nonsense NM_001407751.1:c.4465C>T NP_001394680.1:p.Gln1489Ter nonsense NM_001407752.1:c.4465C>T NP_001394681.1:p.Gln1489Ter nonsense NM_001407838.1:c.4462C>T NP_001394767.1:p.Gln1488Ter nonsense NM_001407839.1:c.4462C>T NP_001394768.1:p.Gln1488Ter nonsense NM_001407841.1:c.4462C>T NP_001394770.1:p.Gln1488Ter nonsense NM_001407842.1:c.4462C>T NP_001394771.1:p.Gln1488Ter nonsense NM_001407843.1:c.4462C>T NP_001394772.1:p.Gln1488Ter nonsense NM_001407844.1:c.4462C>T NP_001394773.1:p.Gln1488Ter nonsense NM_001407845.1:c.4462C>T NP_001394774.1:p.Gln1488Ter nonsense NM_001407846.1:c.4462C>T NP_001394775.1:p.Gln1488Ter nonsense NM_001407847.1:c.4462C>T NP_001394776.1:p.Gln1488Ter nonsense NM_001407848.1:c.4462C>T NP_001394777.1:p.Gln1488Ter nonsense NM_001407849.1:c.4462C>T NP_001394778.1:p.Gln1488Ter nonsense NM_001407850.1:c.4462C>T NP_001394779.1:p.Gln1488Ter nonsense NM_001407851.1:c.4462C>T NP_001394780.1:p.Gln1488Ter nonsense NM_001407852.1:c.4462C>T NP_001394781.1:p.Gln1488Ter nonsense NM_001407853.1:c.4462C>T NP_001394782.1:p.Gln1488Ter nonsense NM_001407854.1:c.4609C>T NP_001394783.1:p.Gln1537Ter nonsense NM_001407858.1:c.4606C>T NP_001394787.1:p.Gln1536Ter nonsense NM_001407859.1:c.4606C>T NP_001394788.1:p.Gln1536Ter nonsense NM_001407860.1:c.4606C>T NP_001394789.1:p.Gln1536Ter nonsense NM_001407861.1:c.4603C>T NP_001394790.1:p.Gln1535Ter nonsense NM_001407862.1:c.4408C>T NP_001394791.1:p.Gln1470Ter nonsense NM_001407863.1:c.4483C>T NP_001394792.1:p.Gln1495Ter nonsense NM_001407874.1:c.4402C>T NP_001394803.1:p.Gln1468Ter nonsense NM_001407875.1:c.4402C>T NP_001394804.1:p.Gln1468Ter nonsense NM_001407879.1:c.4399C>T NP_001394808.1:p.Gln1467Ter nonsense NM_001407881.1:c.4399C>T NP_001394810.1:p.Gln1467Ter nonsense NM_001407882.1:c.4399C>T NP_001394811.1:p.Gln1467Ter nonsense NM_001407884.1:c.4399C>T NP_001394813.1:p.Gln1467Ter nonsense NM_001407885.1:c.4399C>T NP_001394814.1:p.Gln1467Ter nonsense NM_001407886.1:c.4399C>T NP_001394815.1:p.Gln1467Ter nonsense NM_001407887.1:c.4399C>T NP_001394816.1:p.Gln1467Ter nonsense NM_001407889.1:c.4399C>T NP_001394818.1:p.Gln1467Ter nonsense NM_001407894.1:c.4396C>T NP_001394823.1:p.Gln1466Ter nonsense NM_001407895.1:c.4396C>T NP_001394824.1:p.Gln1466Ter nonsense NM_001407896.1:c.4396C>T NP_001394825.1:p.Gln1466Ter nonsense NM_001407897.1:c.4396C>T NP_001394826.1:p.Gln1466Ter nonsense NM_001407898.1:c.4396C>T NP_001394827.1:p.Gln1466Ter nonsense NM_001407899.1:c.4396C>T NP_001394828.1:p.Gln1466Ter nonsense NM_001407900.1:c.4396C>T NP_001394829.1:p.Gln1466Ter nonsense NM_001407902.1:c.4396C>T NP_001394831.1:p.Gln1466Ter nonsense NM_001407904.1:c.4396C>T NP_001394833.1:p.Gln1466Ter nonsense NM_001407906.1:c.4396C>T NP_001394835.1:p.Gln1466Ter nonsense NM_001407907.1:c.4396C>T NP_001394836.1:p.Gln1466Ter nonsense NM_001407908.1:c.4396C>T NP_001394837.1:p.Gln1466Ter nonsense NM_001407909.1:c.4396C>T NP_001394838.1:p.Gln1466Ter nonsense NM_001407910.1:c.4396C>T NP_001394839.1:p.Gln1466Ter nonsense NM_001407915.1:c.4393C>T NP_001394844.1:p.Gln1465Ter nonsense NM_001407916.1:c.4393C>T NP_001394845.1:p.Gln1465Ter nonsense NM_001407917.1:c.4393C>T NP_001394846.1:p.Gln1465Ter nonsense NM_001407918.1:c.4393C>T NP_001394847.1:p.Gln1465Ter nonsense NM_001407919.1:c.4486C>T NP_001394848.1:p.Gln1496Ter nonsense NM_001407920.1:c.4345C>T NP_001394849.1:p.Gln1449Ter nonsense NM_001407921.1:c.4345C>T NP_001394850.1:p.Gln1449Ter nonsense NM_001407922.1:c.4345C>T NP_001394851.1:p.Gln1449Ter nonsense NM_001407923.1:c.4345C>T NP_001394852.1:p.Gln1449Ter nonsense NM_001407924.1:c.4345C>T NP_001394853.1:p.Gln1449Ter nonsense NM_001407925.1:c.4345C>T NP_001394854.1:p.Gln1449Ter nonsense NM_001407926.1:c.4345C>T NP_001394855.1:p.Gln1449Ter nonsense NM_001407927.1:c.4342C>T NP_001394856.1:p.Gln1448Ter nonsense NM_001407928.1:c.4342C>T NP_001394857.1:p.Gln1448Ter nonsense NM_001407929.1:c.4342C>T NP_001394858.1:p.Gln1448Ter nonsense NM_001407930.1:c.4342C>T NP_001394859.1:p.Gln1448Ter nonsense NM_001407931.1:c.4342C>T NP_001394860.1:p.Gln1448Ter nonsense NM_001407932.1:c.4342C>T NP_001394861.1:p.Gln1448Ter nonsense NM_001407933.1:c.4342C>T NP_001394862.1:p.Gln1448Ter nonsense NM_001407934.1:c.4339C>T NP_001394863.1:p.Gln1447Ter nonsense NM_001407935.1:c.4339C>T NP_001394864.1:p.Gln1447Ter nonsense NM_001407936.1:c.4339C>T NP_001394865.1:p.Gln1447Ter nonsense NM_001407937.1:c.4486C>T NP_001394866.1:p.Gln1496Ter nonsense NM_001407938.1:c.4486C>T NP_001394867.1:p.Gln1496Ter nonsense NM_001407939.1:c.4483C>T NP_001394868.1:p.Gln1495Ter nonsense NM_001407940.1:c.4483C>T NP_001394869.1:p.Gln1495Ter nonsense NM_001407941.1:c.4480C>T NP_001394870.1:p.Gln1494Ter nonsense NM_001407942.1:c.4468C>T NP_001394871.1:p.Gln1490Ter nonsense NM_001407943.1:c.4465C>T NP_001394872.1:p.Gln1489Ter nonsense NM_001407944.1:c.4465C>T NP_001394873.1:p.Gln1489Ter nonsense NM_001407945.1:c.4465C>T NP_001394874.1:p.Gln1489Ter nonsense NM_001407946.1:c.4276C>T NP_001394875.1:p.Gln1426Ter nonsense NM_001407947.1:c.4276C>T NP_001394876.1:p.Gln1426Ter nonsense NM_001407948.1:c.4276C>T NP_001394877.1:p.Gln1426Ter nonsense NM_001407949.1:c.4276C>T NP_001394878.1:p.Gln1426Ter nonsense NM_001407950.1:c.4273C>T NP_001394879.1:p.Gln1425Ter nonsense NM_001407951.1:c.4273C>T NP_001394880.1:p.Gln1425Ter nonsense NM_001407952.1:c.4273C>T NP_001394881.1:p.Gln1425Ter nonsense NM_001407953.1:c.4273C>T NP_001394882.1:p.Gln1425Ter nonsense NM_001407954.1:c.4273C>T NP_001394883.1:p.Gln1425Ter nonsense NM_001407955.1:c.4273C>T NP_001394884.1:p.Gln1425Ter nonsense NM_001407956.1:c.4270C>T NP_001394885.1:p.Gln1424Ter nonsense NM_001407957.1:c.4270C>T NP_001394886.1:p.Gln1424Ter nonsense NM_001407958.1:c.4270C>T NP_001394887.1:p.Gln1424Ter nonsense NM_001407959.1:c.4228C>T NP_001394888.1:p.Gln1410Ter nonsense NM_001407960.1:c.4225C>T NP_001394889.1:p.Gln1409Ter nonsense NM_001407962.1:c.4225C>T NP_001394891.1:p.Gln1409Ter nonsense NM_001407963.1:c.4222C>T NP_001394892.1:p.Gln1408Ter nonsense NM_001407965.1:c.4102C>T NP_001394894.1:p.Gln1368Ter nonsense NM_001407966.1:c.3721C>T NP_001394895.1:p.Gln1241Ter nonsense NM_001407967.1:c.3718C>T NP_001394896.1:p.Gln1240Ter nonsense NM_001407968.1:c.2005C>T NP_001394897.1:p.Gln669Ter nonsense NM_001407969.1:c.2002C>T NP_001394898.1:p.Gln668Ter nonsense NM_001407970.1:c.1366C>T NP_001394899.1:p.Gln456Ter nonsense NM_001407971.1:c.1366C>T NP_001394900.1:p.Gln456Ter nonsense NM_001407972.1:c.1363C>T NP_001394901.1:p.Gln455Ter nonsense NM_001407973.1:c.1300C>T NP_001394902.1:p.Gln434Ter nonsense NM_001407974.1:c.1300C>T NP_001394903.1:p.Gln434Ter nonsense NM_001407975.1:c.1300C>T NP_001394904.1:p.Gln434Ter nonsense NM_001407976.1:c.1300C>T NP_001394905.1:p.Gln434Ter nonsense NM_001407977.1:c.1300C>T NP_001394906.1:p.Gln434Ter nonsense NM_001407978.1:c.1300C>T NP_001394907.1:p.Gln434Ter nonsense NM_001407979.1:c.1297C>T NP_001394908.1:p.Gln433Ter nonsense NM_001407980.1:c.1297C>T NP_001394909.1:p.Gln433Ter nonsense NM_001407981.1:c.1297C>T NP_001394910.1:p.Gln433Ter nonsense NM_001407982.1:c.1297C>T NP_001394911.1:p.Gln433Ter nonsense NM_001407983.1:c.1297C>T NP_001394912.1:p.Gln433Ter nonsense NM_001407984.1:c.1297C>T NP_001394913.1:p.Gln433Ter nonsense NM_001407985.1:c.1297C>T NP_001394914.1:p.Gln433Ter nonsense NM_001407986.1:c.1297C>T NP_001394915.1:p.Gln433Ter nonsense NM_001407990.1:c.1297C>T NP_001394919.1:p.Gln433Ter nonsense NM_001407991.1:c.1297C>T NP_001394920.1:p.Gln433Ter nonsense NM_001407992.1:c.1297C>T NP_001394921.1:p.Gln433Ter nonsense NM_001407993.1:c.1297C>T NP_001394922.1:p.Gln433Ter nonsense NM_001408392.1:c.1294C>T NP_001395321.1:p.Gln432Ter nonsense NM_001408396.1:c.1294C>T NP_001395325.1:p.Gln432Ter nonsense NM_001408397.1:c.1294C>T NP_001395326.1:p.Gln432Ter nonsense NM_001408398.1:c.1294C>T NP_001395327.1:p.Gln432Ter nonsense NM_001408399.1:c.1294C>T NP_001395328.1:p.Gln432Ter nonsense NM_001408400.1:c.1294C>T NP_001395329.1:p.Gln432Ter nonsense NM_001408401.1:c.1294C>T NP_001395330.1:p.Gln432Ter nonsense NM_001408402.1:c.1294C>T NP_001395331.1:p.Gln432Ter nonsense NM_001408403.1:c.1294C>T NP_001395332.1:p.Gln432Ter nonsense NM_001408404.1:c.1294C>T NP_001395333.1:p.Gln432Ter nonsense NM_001408406.1:c.1291C>T NP_001395335.1:p.Gln431Ter nonsense NM_001408407.1:c.1291C>T NP_001395336.1:p.Gln431Ter nonsense NM_001408408.1:c.1291C>T NP_001395337.1:p.Gln431Ter nonsense NM_001408409.1:c.1288C>T NP_001395338.1:p.Gln430Ter nonsense NM_001408410.1:c.1225C>T NP_001395339.1:p.Gln409Ter nonsense NM_001408411.1:c.1222C>T NP_001395340.1:p.Gln408Ter nonsense NM_001408412.1:c.1219C>T NP_001395341.1:p.Gln407Ter nonsense NM_001408413.1:c.1219C>T NP_001395342.1:p.Gln407Ter nonsense NM_001408414.1:c.1219C>T NP_001395343.1:p.Gln407Ter nonsense NM_001408415.1:c.1219C>T NP_001395344.1:p.Gln407Ter nonsense NM_001408416.1:c.1219C>T NP_001395345.1:p.Gln407Ter nonsense NM_001408418.1:c.1183C>T NP_001395347.1:p.Gln395Ter nonsense NM_001408419.1:c.1183C>T NP_001395348.1:p.Gln395Ter nonsense NM_001408420.1:c.1183C>T NP_001395349.1:p.Gln395Ter nonsense NM_001408421.1:c.1180C>T NP_001395350.1:p.Gln394Ter nonsense NM_001408422.1:c.1180C>T NP_001395351.1:p.Gln394Ter nonsense NM_001408423.1:c.1180C>T NP_001395352.1:p.Gln394Ter nonsense NM_001408424.1:c.1180C>T NP_001395353.1:p.Gln394Ter nonsense NM_001408425.1:c.1177C>T NP_001395354.1:p.Gln393Ter nonsense NM_001408426.1:c.1177C>T NP_001395355.1:p.Gln393Ter nonsense NM_001408427.1:c.1177C>T NP_001395356.1:p.Gln393Ter nonsense NM_001408428.1:c.1177C>T NP_001395357.1:p.Gln393Ter nonsense NM_001408429.1:c.1177C>T NP_001395358.1:p.Gln393Ter nonsense NM_001408430.1:c.1177C>T NP_001395359.1:p.Gln393Ter nonsense NM_001408431.1:c.1177C>T NP_001395360.1:p.Gln393Ter nonsense NM_001408432.1:c.1174C>T NP_001395361.1:p.Gln392Ter nonsense NM_001408433.1:c.1174C>T NP_001395362.1:p.Gln392Ter nonsense NM_001408434.1:c.1174C>T NP_001395363.1:p.Gln392Ter nonsense NM_001408435.1:c.1174C>T NP_001395364.1:p.Gln392Ter nonsense NM_001408436.1:c.1174C>T NP_001395365.1:p.Gln392Ter nonsense NM_001408437.1:c.1174C>T NP_001395366.1:p.Gln392Ter nonsense NM_001408438.1:c.1174C>T NP_001395367.1:p.Gln392Ter nonsense NM_001408439.1:c.1174C>T NP_001395368.1:p.Gln392Ter nonsense NM_001408440.1:c.1174C>T NP_001395369.1:p.Gln392Ter nonsense NM_001408441.1:c.1174C>T NP_001395370.1:p.Gln392Ter nonsense NM_001408442.1:c.1174C>T NP_001395371.1:p.Gln392Ter nonsense NM_001408443.1:c.1174C>T NP_001395372.1:p.Gln392Ter nonsense NM_001408444.1:c.1174C>T NP_001395373.1:p.Gln392Ter nonsense NM_001408445.1:c.1171C>T NP_001395374.1:p.Gln391Ter nonsense NM_001408446.1:c.1171C>T NP_001395375.1:p.Gln391Ter nonsense NM_001408447.1:c.1171C>T NP_001395376.1:p.Gln391Ter nonsense NM_001408448.1:c.1171C>T NP_001395377.1:p.Gln391Ter nonsense NM_001408450.1:c.1171C>T NP_001395379.1:p.Gln391Ter nonsense NM_001408451.1:c.1165C>T NP_001395380.1:p.Gln389Ter nonsense NM_001408452.1:c.1159C>T NP_001395381.1:p.Gln387Ter nonsense NM_001408453.1:c.1159C>T NP_001395382.1:p.Gln387Ter nonsense NM_001408454.1:c.1159C>T NP_001395383.1:p.Gln387Ter nonsense NM_001408455.1:c.1159C>T NP_001395384.1:p.Gln387Ter nonsense NM_001408456.1:c.1159C>T NP_001395385.1:p.Gln387Ter nonsense NM_001408457.1:c.1159C>T NP_001395386.1:p.Gln387Ter nonsense NM_001408458.1:c.1156C>T NP_001395387.1:p.Gln386Ter nonsense NM_001408459.1:c.1156C>T NP_001395388.1:p.Gln386Ter nonsense NM_001408460.1:c.1156C>T NP_001395389.1:p.Gln386Ter nonsense NM_001408461.1:c.1156C>T NP_001395390.1:p.Gln386Ter nonsense NM_001408462.1:c.1156C>T NP_001395391.1:p.Gln386Ter nonsense NM_001408463.1:c.1156C>T NP_001395392.1:p.Gln386Ter nonsense NM_001408464.1:c.1156C>T NP_001395393.1:p.Gln386Ter nonsense NM_001408465.1:c.1156C>T NP_001395394.1:p.Gln386Ter nonsense NM_001408466.1:c.1156C>T NP_001395395.1:p.Gln386Ter nonsense NM_001408467.1:c.1156C>T NP_001395396.1:p.Gln386Ter nonsense NM_001408468.1:c.1153C>T NP_001395397.1:p.Gln385Ter nonsense NM_001408469.1:c.1153C>T NP_001395398.1:p.Gln385Ter nonsense NM_001408470.1:c.1153C>T NP_001395399.1:p.Gln385Ter nonsense NM_001408472.1:c.1297C>T NP_001395401.1:p.Gln433Ter nonsense NM_001408473.1:c.1294C>T NP_001395402.1:p.Gln432Ter nonsense NM_001408474.1:c.1099C>T NP_001395403.1:p.Gln367Ter nonsense NM_001408475.1:c.1096C>T NP_001395404.1:p.Gln366Ter nonsense NM_001408476.1:c.1096C>T NP_001395405.1:p.Gln366Ter nonsense NM_001408478.1:c.1090C>T NP_001395407.1:p.Gln364Ter nonsense NM_001408479.1:c.1090C>T NP_001395408.1:p.Gln364Ter nonsense NM_001408480.1:c.1090C>T NP_001395409.1:p.Gln364Ter nonsense NM_001408481.1:c.1087C>T NP_001395410.1:p.Gln363Ter nonsense NM_001408482.1:c.1087C>T NP_001395411.1:p.Gln363Ter nonsense NM_001408483.1:c.1087C>T NP_001395412.1:p.Gln363Ter nonsense NM_001408484.1:c.1087C>T NP_001395413.1:p.Gln363Ter nonsense NM_001408485.1:c.1087C>T NP_001395414.1:p.Gln363Ter nonsense NM_001408489.1:c.1087C>T NP_001395418.1:p.Gln363Ter nonsense NM_001408490.1:c.1087C>T NP_001395419.1:p.Gln363Ter nonsense NM_001408491.1:c.1087C>T NP_001395420.1:p.Gln363Ter nonsense NM_001408492.1:c.1084C>T NP_001395421.1:p.Gln362Ter nonsense NM_001408493.1:c.1084C>T NP_001395422.1:p.Gln362Ter nonsense NM_001408494.1:c.1060C>T NP_001395423.1:p.Gln354Ter nonsense NM_001408495.1:c.1054C>T NP_001395424.1:p.Gln352Ter nonsense NM_001408496.1:c.1036C>T NP_001395425.1:p.Gln346Ter nonsense NM_001408497.1:c.1036C>T NP_001395426.1:p.Gln346Ter nonsense NM_001408498.1:c.1036C>T NP_001395427.1:p.Gln346Ter nonsense NM_001408499.1:c.1036C>T NP_001395428.1:p.Gln346Ter nonsense NM_001408500.1:c.1036C>T NP_001395429.1:p.Gln346Ter nonsense NM_001408501.1:c.1036C>T NP_001395430.1:p.Gln346Ter nonsense NM_001408502.1:c.1033C>T NP_001395431.1:p.Gln345Ter nonsense NM_001408503.1:c.1033C>T NP_001395432.1:p.Gln345Ter nonsense NM_001408504.1:c.1033C>T NP_001395433.1:p.Gln345Ter nonsense NM_001408505.1:c.1030C>T NP_001395434.1:p.Gln344Ter nonsense NM_001408506.1:c.973C>T NP_001395435.1:p.Gln325Ter nonsense NM_001408507.1:c.970C>T NP_001395436.1:p.Gln324Ter nonsense NM_001408508.1:c.961C>T NP_001395437.1:p.Gln321Ter nonsense NM_001408509.1:c.958C>T NP_001395438.1:p.Gln320Ter nonsense NM_001408510.1:c.919C>T NP_001395439.1:p.Gln307Ter nonsense NM_001408511.1:c.916C>T NP_001395440.1:p.Gln306Ter nonsense NM_001408512.1:c.796C>T NP_001395441.1:p.Gln266Ter nonsense NM_007297.4:c.4468C>T NP_009228.2:p.Gln1490Ter nonsense NM_007298.4:c.1297C>T NP_009229.2:p.Gln433Ter nonsense NM_007299.4:c.1297C>T NP_009230.2:p.Gln433Ter nonsense NM_007300.4:c.4672C>T NP_009231.2:p.Gln1558Ter nonsense NM_007304.2:c.1297C>T NP_009235.2:p.Gln433Ter nonsense NR_027676.2:n.4786C>T non-coding transcript variant NC_000017.11:g.43074397G>A NC_000017.10:g.41226414G>A NG_005905.2:g.143587C>T LRG_292:g.143587C>T LRG_292t1:c.4609C>T LRG_292p1:p.Gln1537Ter U14680.1:n.4728C>T - Protein change
- Q1537*, Q1490*, Q433*, Q1558*, Q1368*, Q1425*, Q1447*, Q1467*, Q1494*, Q1495*, Q1510*, Q1518*, Q1533*, Q1535*, Q1557*, Q1559*, Q266*, Q321*, Q325*, Q345*, Q352*, Q354*, Q386*, Q392*, Q409*, Q456*, Q668*, Q1240*, Q1408*, Q1466*, Q1468*, Q1488*, Q1532*, Q306*, Q307*, Q364*, Q366*, Q367*, Q385*, Q395*, Q407*, Q431*, Q432*, Q455*, Q1409*, Q1426*, Q1448*, Q1449*, Q1465*, Q1470*, Q1511*, Q1534*, Q320*, Q344*, Q362*, Q387*, Q389*, Q391*, Q394*, Q434*, Q1241*, Q1410*, Q1424*, Q1489*, Q1493*, Q1496*, Q1509*, Q1517*, Q1536*, Q324*, Q346*, Q363*, Q393*, Q408*, Q430*, Q669*
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074396:G: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.
- -
- 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 |
13041 | 14847 | |
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 (5) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000112363.15 | |
| Pathogenic (2) |
criteria provided, single submitter
|
May 24, 2018 | RCV000479214.11 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 23, 2023 | RCV000496357.17 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Sep 28, 2022 | RCV000509797.11 |
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)
|
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: SCV000300142.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
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: SCV000326007.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Dec 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
inherited
|
Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000746293.1
First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016 |
Geographic origin: Iran
|
|
|
Pathogenic
(May 24, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000564740.3
First in ClinVar: Apr 27, 2017 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted BRCA1 c.4609C>T at the cDNA level and p.Gln1537Ter (Q1537X) at the protein level. The substitution creates a nonsense variant, which changes … (more)
This variant is denoted BRCA1 c.4609C>T at the cDNA level and p.Gln1537Ter (Q1537X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as c.4728C>T, has been observed in association with breast and/or ovarian cancer (Ozcelik 2003, Yassaee 2016) and is considered pathogenic. (less)
|
|
|
Pathogenic
(Feb 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001588703.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55237). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55237). This variant is also known as p.Q1537X (c.4728C>T). This premature translational stop signal has been observed in individual(s) with breast cancer and ovarian (PMID: 12920083, 27165220, 30078507). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1537*) 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). (less)
|
|
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Pathogenic
(Sep 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000608084.5
First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024 |
Comment:
The p.Q1537* pathogenic mutation (also known as c.4609C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at … (more)
The p.Q1537* pathogenic mutation (also known as c.4609C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4609. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This pathogenic mutation, designated as 4728C>T, has been reported in one individual diagnosed with invasive breast cancer (Ozcelik H et al. J Med Genet. 2003 Aug;40(8):e91). This mutation has also been identified in a patient of Iranian ethnicity with both a personal and family history of breast and/or ovarian cancers (Yassaee VR et al. Asian Pac J Cancer Prev. 2016;17(S3):149-53). 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)
|
|
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Pathogenic
(Oct 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
unknown
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV005045696.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
The c.4609C>T (p.Gln1537*) variant in the BRCA1 gene is located on the exon 14 and introduces an early stop codon. It is predicted to result … (more)
The c.4609C>T (p.Gln1537*) variant in the BRCA1 gene is located on the exon 14 and introduces an early stop codon. It is predicted to result in an absent or disrupted protein product. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 12920083, 27165220, 30078507). This variant is absent in the general population database, gnomAD. The variant is reported in ClinVar as pathogenic (ID: 55237) and reviewed by the expert panel. Truncating variants in the BRCA1 gene are known to be pathogenic (PMID: 21989022, 17661172, 22762150). Therefore, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Dec 23, 2003)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145127.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern
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Pathogenic
(Feb 08, 2008)
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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: SCV000297613.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
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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: SCV000587412.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552263.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
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Comment:
Comment:
This variant is denoted BRCA1 c.4609C>T at the cDNA level and p.Gln1537Ter (Q1537X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as c.4728C>T, has been observed in association with breast and/or ovarian cancer (Ozcelik 2003, Yassaee 2016) and is considered pathogenic.
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55237). This variant is also known as p.Q1537X (c.4728C>T). This premature translational stop signal has been observed in individual(s) with breast cancer and ovarian (PMID: 12920083, 27165220, 30078507). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1537*) 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).
Comment:
The p.Q1537* pathogenic mutation (also known as c.4609C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4609. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This pathogenic mutation, designated as 4728C>T, has been reported in one individual diagnosed with invasive breast cancer (Ozcelik H et al. J Med Genet. 2003 Aug;40(8):e91). This mutation has also been identified in a patient of Iranian ethnicity with both a personal and family history of breast and/or ovarian cancers (Yassaee VR et al. Asian Pac J Cancer Prev. 2016;17(S3):149-53). 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:
The c.4609C>T (p.Gln1537*) variant in the BRCA1 gene is located on the exon 14 and introduces an early stop codon. It is predicted to result in an absent or disrupted protein product. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 12920083, 27165220, 30078507). This variant is absent in the general population database, gnomAD. The variant is reported in ClinVar as pathogenic (ID: 55237) and reviewed by the expert panel. Truncating variants in the BRCA1 gene are known to be pathogenic (PMID: 21989022, 17661172, 22762150). Therefore, this variant is classified as pathogenic.
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:
This variant is denoted BRCA1 c.4609C>T at the cDNA level and p.Gln1537Ter (Q1537X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously reported as c.4728C>T, has been observed in association with breast and/or ovarian cancer (Ozcelik 2003, Yassaee 2016) and is considered pathogenic.
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55237). This variant is also known as p.Q1537X (c.4728C>T). This premature translational stop signal has been observed in individual(s) with breast cancer and ovarian (PMID: 12920083, 27165220, 30078507). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1537*) 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).
Comment:
The p.Q1537* pathogenic mutation (also known as c.4609C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4609. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This pathogenic mutation, designated as 4728C>T, has been reported in one individual diagnosed with invasive breast cancer (Ozcelik H et al. J Med Genet. 2003 Aug;40(8):e91). This mutation has also been identified in a patient of Iranian ethnicity with both a personal and family history of breast and/or ovarian cancers (Yassaee VR et al. Asian Pac J Cancer Prev. 2016;17(S3):149-53). 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:
The c.4609C>T (p.Gln1537*) variant in the BRCA1 gene is located on the exon 14 and introduces an early stop codon. It is predicted to result in an absent or disrupted protein product. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 12920083, 27165220, 30078507). This variant is absent in the general population database, gnomAD. The variant is reported in ClinVar as pathogenic (ID: 55237) and reviewed by the expert panel. Truncating variants in the BRCA1 gene are known to be pathogenic (PMID: 21989022, 17661172, 22762150). Therefore, this variant is classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
| Mutation Spectra of BRCA Genes in Iranian Women with Early Onset Breast Cancer - 15 Years Experience. | Yassaee VR | Asian Pacific journal of cancer prevention : APJCP | 2016 | PMID: 27165220 |
| 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 |
| Individual and family characteristics associated with protein truncating BRCA1 and BRCA2 mutations in an Ontario population based series from the Cooperative Family Registry for Breast Cancer Studies. | Ozcelik H | Journal of medical genetics | 2003 | PMID: 12920083 |
Text-mined citations for rs80357229 ...
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 03, 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.