Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5335C>T (p.Gln1779Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Oct 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.5335C>T (p.Gln1779Ter)
Variation ID: 55540 Accession: VCV000055540.20
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43049192 (GRCh38) [ NCBI UCSC ] 17: 41201209 (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 Oct 22, 2016 May 1, 2024 Oct 18, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5335C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln1779Ter nonsense NM_001407571.1:c.5122C>T NP_001394500.1:p.Gln1708Ter nonsense NM_001407581.1:c.5401C>T NP_001394510.1:p.Gln1801Ter nonsense NM_001407582.1:c.5401C>T NP_001394511.1:p.Gln1801Ter nonsense NM_001407583.1:c.5398C>T NP_001394512.1:p.Gln1800Ter nonsense NM_001407585.1:c.5398C>T NP_001394514.1:p.Gln1800Ter nonsense NM_001407587.1:c.5398C>T NP_001394516.1:p.Gln1800Ter nonsense NM_001407590.1:c.5395C>T NP_001394519.1:p.Gln1799Ter nonsense NM_001407591.1:c.5395C>T NP_001394520.1:p.Gln1799Ter nonsense NM_001407593.1:c.5335C>T NP_001394522.1:p.Gln1779Ter nonsense NM_001407594.1:c.5335C>T NP_001394523.1:p.Gln1779Ter nonsense NM_001407596.1:c.5335C>T NP_001394525.1:p.Gln1779Ter nonsense NM_001407597.1:c.5335C>T NP_001394526.1:p.Gln1779Ter nonsense NM_001407598.1:c.5335C>T NP_001394527.1:p.Gln1779Ter nonsense NM_001407602.1:c.5335C>T NP_001394531.1:p.Gln1779Ter nonsense NM_001407603.1:c.5335C>T NP_001394532.1:p.Gln1779Ter nonsense NM_001407605.1:c.5335C>T NP_001394534.1:p.Gln1779Ter nonsense NM_001407610.1:c.5332C>T NP_001394539.1:p.Gln1778Ter nonsense NM_001407611.1:c.5332C>T NP_001394540.1:p.Gln1778Ter nonsense NM_001407612.1:c.5332C>T NP_001394541.1:p.Gln1778Ter nonsense NM_001407613.1:c.5332C>T NP_001394542.1:p.Gln1778Ter nonsense NM_001407614.1:c.5332C>T NP_001394543.1:p.Gln1778Ter nonsense NM_001407615.1:c.5332C>T NP_001394544.1:p.Gln1778Ter nonsense NM_001407616.1:c.5332C>T NP_001394545.1:p.Gln1778Ter nonsense NM_001407617.1:c.5332C>T NP_001394546.1:p.Gln1778Ter nonsense NM_001407618.1:c.5332C>T NP_001394547.1:p.Gln1778Ter nonsense NM_001407619.1:c.5332C>T NP_001394548.1:p.Gln1778Ter nonsense NM_001407620.1:c.5332C>T NP_001394549.1:p.Gln1778Ter nonsense NM_001407621.1:c.5332C>T NP_001394550.1:p.Gln1778Ter nonsense NM_001407622.1:c.5332C>T NP_001394551.1:p.Gln1778Ter nonsense NM_001407623.1:c.5332C>T NP_001394552.1:p.Gln1778Ter nonsense NM_001407624.1:c.5332C>T NP_001394553.1:p.Gln1778Ter nonsense NM_001407625.1:c.5332C>T NP_001394554.1:p.Gln1778Ter nonsense NM_001407626.1:c.5332C>T NP_001394555.1:p.Gln1778Ter nonsense NM_001407627.1:c.5329C>T NP_001394556.1:p.Gln1777Ter nonsense NM_001407628.1:c.5329C>T NP_001394557.1:p.Gln1777Ter nonsense NM_001407629.1:c.5329C>T NP_001394558.1:p.Gln1777Ter nonsense NM_001407630.1:c.5329C>T NP_001394559.1:p.Gln1777Ter nonsense NM_001407631.1:c.5329C>T NP_001394560.1:p.Gln1777Ter nonsense NM_001407632.1:c.5329C>T NP_001394561.1:p.Gln1777Ter nonsense NM_001407633.1:c.5329C>T NP_001394562.1:p.Gln1777Ter nonsense NM_001407634.1:c.5329C>T NP_001394563.1:p.Gln1777Ter nonsense NM_001407635.1:c.5329C>T NP_001394564.1:p.Gln1777Ter nonsense NM_001407636.1:c.5329C>T NP_001394565.1:p.Gln1777Ter nonsense NM_001407637.1:c.5329C>T NP_001394566.1:p.Gln1777Ter nonsense NM_001407638.1:c.5329C>T NP_001394567.1:p.Gln1777Ter nonsense NM_001407639.1:c.5329C>T NP_001394568.1:p.Gln1777Ter nonsense NM_001407640.1:c.5329C>T NP_001394569.1:p.Gln1777Ter nonsense NM_001407641.1:c.5329C>T NP_001394570.1:p.Gln1777Ter nonsense NM_001407642.1:c.5329C>T NP_001394571.1:p.Gln1777Ter nonsense NM_001407644.1:c.5326C>T NP_001394573.1:p.Gln1776Ter nonsense NM_001407645.1:c.5326C>T NP_001394574.1:p.Gln1776Ter nonsense NM_001407646.1:c.5323C>T NP_001394575.1:p.Gln1775Ter nonsense NM_001407647.1:c.5320C>T NP_001394576.1:p.Gln1774Ter nonsense NM_001407648.1:c.5278C>T NP_001394577.1:p.Gln1760Ter nonsense NM_001407649.1:c.5275C>T NP_001394578.1:p.Gln1759Ter nonsense NM_001407652.1:c.5257C>T NP_001394581.1:p.Gln1753Ter nonsense NM_001407653.1:c.5257C>T NP_001394582.1:p.Gln1753Ter nonsense NM_001407654.1:c.5257C>T NP_001394583.1:p.Gln1753Ter nonsense NM_001407655.1:c.5257C>T NP_001394584.1:p.Gln1753Ter nonsense NM_001407656.1:c.5254C>T NP_001394585.1:p.Gln1752Ter nonsense NM_001407657.1:c.5254C>T NP_001394586.1:p.Gln1752Ter nonsense NM_001407658.1:c.5254C>T NP_001394587.1:p.Gln1752Ter nonsense NM_001407659.1:c.5251C>T NP_001394588.1:p.Gln1751Ter nonsense NM_001407660.1:c.5251C>T NP_001394589.1:p.Gln1751Ter nonsense NM_001407661.1:c.5251C>T NP_001394590.1:p.Gln1751Ter nonsense NM_001407662.1:c.5251C>T NP_001394591.1:p.Gln1751Ter nonsense NM_001407663.1:c.5251C>T NP_001394592.1:p.Gln1751Ter nonsense NM_001407664.1:c.5212C>T NP_001394593.1:p.Gln1738Ter nonsense NM_001407665.1:c.5212C>T NP_001394594.1:p.Gln1738Ter nonsense NM_001407666.1:c.5212C>T NP_001394595.1:p.Gln1738Ter nonsense NM_001407667.1:c.5212C>T NP_001394596.1:p.Gln1738Ter nonsense NM_001407668.1:c.5212C>T NP_001394597.1:p.Gln1738Ter nonsense NM_001407669.1:c.5212C>T NP_001394598.1:p.Gln1738Ter nonsense NM_001407670.1:c.5209C>T NP_001394599.1:p.Gln1737Ter nonsense NM_001407671.1:c.5209C>T NP_001394600.1:p.Gln1737Ter nonsense NM_001407672.1:c.5209C>T NP_001394601.1:p.Gln1737Ter nonsense NM_001407673.1:c.5209C>T NP_001394602.1:p.Gln1737Ter nonsense NM_001407674.1:c.5209C>T NP_001394603.1:p.Gln1737Ter nonsense NM_001407675.1:c.5209C>T NP_001394604.1:p.Gln1737Ter nonsense NM_001407676.1:c.5209C>T NP_001394605.1:p.Gln1737Ter nonsense NM_001407677.1:c.5209C>T NP_001394606.1:p.Gln1737Ter nonsense NM_001407678.1:c.5209C>T NP_001394607.1:p.Gln1737Ter nonsense NM_001407679.1:c.5209C>T NP_001394608.1:p.Gln1737Ter nonsense NM_001407680.1:c.5209C>T NP_001394609.1:p.Gln1737Ter nonsense NM_001407681.1:c.5206C>T NP_001394610.1:p.Gln1736Ter nonsense NM_001407682.1:c.5206C>T NP_001394611.1:p.Gln1736Ter nonsense NM_001407683.1:c.5206C>T NP_001394612.1:p.Gln1736Ter nonsense NM_001407685.1:c.5206C>T NP_001394614.1:p.Gln1736Ter nonsense NM_001407686.1:c.5206C>T NP_001394615.1:p.Gln1736Ter nonsense NM_001407687.1:c.5206C>T NP_001394616.1:p.Gln1736Ter nonsense NM_001407688.1:c.5206C>T NP_001394617.1:p.Gln1736Ter nonsense NM_001407689.1:c.5206C>T NP_001394618.1:p.Gln1736Ter nonsense NM_001407690.1:c.5203C>T NP_001394619.1:p.Gln1735Ter nonsense NM_001407691.1:c.5203C>T NP_001394620.1:p.Gln1735Ter nonsense NM_001407692.1:c.5194C>T NP_001394621.1:p.Gln1732Ter nonsense NM_001407694.1:c.5194C>T NP_001394623.1:p.Gln1732Ter nonsense NM_001407695.1:c.5194C>T NP_001394624.1:p.Gln1732Ter nonsense NM_001407696.1:c.5194C>T NP_001394625.1:p.Gln1732Ter nonsense NM_001407697.1:c.5194C>T NP_001394626.1:p.Gln1732Ter nonsense NM_001407698.1:c.5194C>T NP_001394627.1:p.Gln1732Ter nonsense NM_001407724.1:c.5194C>T NP_001394653.1:p.Gln1732Ter nonsense NM_001407725.1:c.5194C>T NP_001394654.1:p.Gln1732Ter nonsense NM_001407726.1:c.5194C>T NP_001394655.1:p.Gln1732Ter nonsense NM_001407727.1:c.5194C>T NP_001394656.1:p.Gln1732Ter nonsense NM_001407728.1:c.5194C>T NP_001394657.1:p.Gln1732Ter nonsense NM_001407729.1:c.5194C>T NP_001394658.1:p.Gln1732Ter nonsense NM_001407730.1:c.5194C>T NP_001394659.1:p.Gln1732Ter nonsense NM_001407731.1:c.5194C>T NP_001394660.1:p.Gln1732Ter nonsense NM_001407732.1:c.5191C>T NP_001394661.1:p.Gln1731Ter nonsense NM_001407733.1:c.5191C>T NP_001394662.1:p.Gln1731Ter nonsense NM_001407734.1:c.5191C>T NP_001394663.1:p.Gln1731Ter nonsense NM_001407735.1:c.5191C>T NP_001394664.1:p.Gln1731Ter nonsense NM_001407736.1:c.5191C>T NP_001394665.1:p.Gln1731Ter nonsense NM_001407737.1:c.5191C>T NP_001394666.1:p.Gln1731Ter nonsense NM_001407738.1:c.5191C>T NP_001394667.1:p.Gln1731Ter nonsense NM_001407739.1:c.5191C>T NP_001394668.1:p.Gln1731Ter nonsense NM_001407740.1:c.5191C>T NP_001394669.1:p.Gln1731Ter nonsense NM_001407741.1:c.5191C>T NP_001394670.1:p.Gln1731Ter nonsense NM_001407742.1:c.5191C>T NP_001394671.1:p.Gln1731Ter nonsense NM_001407743.1:c.5191C>T NP_001394672.1:p.Gln1731Ter nonsense NM_001407744.1:c.5191C>T NP_001394673.1:p.Gln1731Ter nonsense NM_001407745.1:c.5191C>T NP_001394674.1:p.Gln1731Ter nonsense NM_001407746.1:c.5191C>T NP_001394675.1:p.Gln1731Ter nonsense NM_001407747.1:c.5191C>T NP_001394676.1:p.Gln1731Ter nonsense NM_001407748.1:c.5191C>T NP_001394677.1:p.Gln1731Ter nonsense NM_001407749.1:c.5191C>T NP_001394678.1:p.Gln1731Ter nonsense NM_001407750.1:c.5191C>T NP_001394679.1:p.Gln1731Ter nonsense NM_001407751.1:c.5191C>T NP_001394680.1:p.Gln1731Ter nonsense NM_001407752.1:c.5191C>T NP_001394681.1:p.Gln1731Ter nonsense NM_001407838.1:c.5188C>T NP_001394767.1:p.Gln1730Ter nonsense NM_001407839.1:c.5188C>T NP_001394768.1:p.Gln1730Ter nonsense NM_001407841.1:c.5188C>T NP_001394770.1:p.Gln1730Ter nonsense NM_001407842.1:c.5188C>T NP_001394771.1:p.Gln1730Ter nonsense NM_001407843.1:c.5188C>T NP_001394772.1:p.Gln1730Ter nonsense NM_001407844.1:c.5188C>T NP_001394773.1:p.Gln1730Ter nonsense NM_001407845.1:c.5188C>T NP_001394774.1:p.Gln1730Ter nonsense NM_001407846.1:c.5188C>T NP_001394775.1:p.Gln1730Ter nonsense NM_001407847.1:c.5188C>T NP_001394776.1:p.Gln1730Ter nonsense NM_001407848.1:c.5188C>T NP_001394777.1:p.Gln1730Ter nonsense NM_001407849.1:c.5188C>T NP_001394778.1:p.Gln1730Ter nonsense NM_001407850.1:c.5188C>T NP_001394779.1:p.Gln1730Ter nonsense NM_001407851.1:c.5188C>T NP_001394780.1:p.Gln1730Ter nonsense NM_001407852.1:c.5188C>T NP_001394781.1:p.Gln1730Ter nonsense NM_001407853.1:c.5188C>T NP_001394782.1:p.Gln1730Ter nonsense NM_001407862.1:c.5134C>T NP_001394791.1:p.Gln1712Ter nonsense NM_001407863.1:c.5131C>T NP_001394792.1:p.Gln1711Ter nonsense NM_001407874.1:c.5128C>T NP_001394803.1:p.Gln1710Ter nonsense NM_001407875.1:c.5128C>T NP_001394804.1:p.Gln1710Ter nonsense NM_001407879.1:c.5125C>T NP_001394808.1:p.Gln1709Ter nonsense NM_001407881.1:c.5125C>T NP_001394810.1:p.Gln1709Ter nonsense NM_001407882.1:c.5125C>T NP_001394811.1:p.Gln1709Ter nonsense NM_001407884.1:c.5125C>T NP_001394813.1:p.Gln1709Ter nonsense NM_001407885.1:c.5125C>T NP_001394814.1:p.Gln1709Ter nonsense NM_001407886.1:c.5125C>T NP_001394815.1:p.Gln1709Ter nonsense NM_001407887.1:c.5125C>T NP_001394816.1:p.Gln1709Ter nonsense NM_001407889.1:c.5125C>T NP_001394818.1:p.Gln1709Ter nonsense NM_001407894.1:c.5122C>T NP_001394823.1:p.Gln1708Ter nonsense NM_001407895.1:c.5122C>T NP_001394824.1:p.Gln1708Ter nonsense NM_001407896.1:c.5122C>T NP_001394825.1:p.Gln1708Ter nonsense NM_001407897.1:c.5122C>T NP_001394826.1:p.Gln1708Ter nonsense NM_001407898.1:c.5122C>T NP_001394827.1:p.Gln1708Ter nonsense NM_001407899.1:c.5122C>T NP_001394828.1:p.Gln1708Ter nonsense NM_001407900.1:c.5122C>T NP_001394829.1:p.Gln1708Ter nonsense NM_001407902.1:c.5122C>T NP_001394831.1:p.Gln1708Ter nonsense NM_001407904.1:c.5122C>T NP_001394833.1:p.Gln1708Ter nonsense NM_001407906.1:c.5122C>T NP_001394835.1:p.Gln1708Ter nonsense NM_001407907.1:c.5122C>T NP_001394836.1:p.Gln1708Ter nonsense NM_001407908.1:c.5122C>T NP_001394837.1:p.Gln1708Ter nonsense NM_001407909.1:c.5122C>T NP_001394838.1:p.Gln1708Ter nonsense NM_001407910.1:c.5122C>T NP_001394839.1:p.Gln1708Ter nonsense NM_001407915.1:c.5119C>T NP_001394844.1:p.Gln1707Ter nonsense NM_001407916.1:c.5119C>T NP_001394845.1:p.Gln1707Ter nonsense NM_001407917.1:c.5119C>T NP_001394846.1:p.Gln1707Ter nonsense NM_001407918.1:c.5119C>T NP_001394847.1:p.Gln1707Ter nonsense NM_001407920.1:c.5071C>T NP_001394849.1:p.Gln1691Ter nonsense NM_001407921.1:c.5071C>T NP_001394850.1:p.Gln1691Ter nonsense NM_001407922.1:c.5071C>T NP_001394851.1:p.Gln1691Ter nonsense NM_001407923.1:c.5071C>T NP_001394852.1:p.Gln1691Ter nonsense NM_001407924.1:c.5071C>T NP_001394853.1:p.Gln1691Ter nonsense NM_001407925.1:c.5071C>T NP_001394854.1:p.Gln1691Ter nonsense NM_001407926.1:c.5071C>T NP_001394855.1:p.Gln1691Ter nonsense NM_001407927.1:c.5068C>T NP_001394856.1:p.Gln1690Ter nonsense NM_001407928.1:c.5068C>T NP_001394857.1:p.Gln1690Ter nonsense NM_001407929.1:c.5068C>T NP_001394858.1:p.Gln1690Ter nonsense NM_001407930.1:c.5068C>T NP_001394859.1:p.Gln1690Ter nonsense NM_001407931.1:c.5068C>T NP_001394860.1:p.Gln1690Ter nonsense NM_001407932.1:c.5068C>T NP_001394861.1:p.Gln1690Ter nonsense NM_001407933.1:c.5068C>T NP_001394862.1:p.Gln1690Ter nonsense NM_001407934.1:c.5065C>T NP_001394863.1:p.Gln1689Ter nonsense NM_001407935.1:c.5065C>T NP_001394864.1:p.Gln1689Ter nonsense NM_001407936.1:c.5065C>T NP_001394865.1:p.Gln1689Ter nonsense NM_001407946.1:c.5002C>T NP_001394875.1:p.Gln1668Ter nonsense NM_001407947.1:c.5002C>T NP_001394876.1:p.Gln1668Ter nonsense NM_001407948.1:c.5002C>T NP_001394877.1:p.Gln1668Ter nonsense NM_001407949.1:c.5002C>T NP_001394878.1:p.Gln1668Ter nonsense NM_001407950.1:c.4999C>T NP_001394879.1:p.Gln1667Ter nonsense NM_001407951.1:c.4999C>T NP_001394880.1:p.Gln1667Ter nonsense NM_001407952.1:c.4999C>T NP_001394881.1:p.Gln1667Ter nonsense NM_001407953.1:c.4999C>T NP_001394882.1:p.Gln1667Ter nonsense NM_001407954.1:c.4999C>T NP_001394883.1:p.Gln1667Ter nonsense NM_001407955.1:c.4999C>T NP_001394884.1:p.Gln1667Ter nonsense NM_001407956.1:c.4996C>T NP_001394885.1:p.Gln1666Ter nonsense NM_001407957.1:c.4996C>T NP_001394886.1:p.Gln1666Ter nonsense NM_001407958.1:c.4996C>T NP_001394887.1:p.Gln1666Ter nonsense NM_001407959.1:c.4954C>T NP_001394888.1:p.Gln1652Ter nonsense NM_001407960.1:c.4951C>T NP_001394889.1:p.Gln1651Ter nonsense NM_001407962.1:c.4951C>T NP_001394891.1:p.Gln1651Ter nonsense NM_001407963.1:c.4948C>T NP_001394892.1:p.Gln1650Ter nonsense NM_001407964.1:c.4873C>T NP_001394893.1:p.Gln1625Ter nonsense NM_001407965.1:c.4828C>T NP_001394894.1:p.Gln1610Ter nonsense NM_001407966.1:c.4447C>T NP_001394895.1:p.Gln1483Ter nonsense NM_001407967.1:c.4444C>T NP_001394896.1:p.Gln1482Ter nonsense NM_001407968.1:c.2731C>T NP_001394897.1:p.Gln911Ter nonsense NM_001407969.1:c.2728C>T NP_001394898.1:p.Gln910Ter nonsense NM_001407970.1:c.2092C>T NP_001394899.1:p.Gln698Ter nonsense NM_001407971.1:c.2092C>T NP_001394900.1:p.Gln698Ter nonsense NM_001407972.1:c.2089C>T NP_001394901.1:p.Gln697Ter nonsense NM_001407973.1:c.2026C>T NP_001394902.1:p.Gln676Ter nonsense NM_001407974.1:c.2026C>T NP_001394903.1:p.Gln676Ter nonsense NM_001407975.1:c.2026C>T NP_001394904.1:p.Gln676Ter nonsense NM_001407976.1:c.2026C>T NP_001394905.1:p.Gln676Ter nonsense NM_001407977.1:c.2026C>T NP_001394906.1:p.Gln676Ter nonsense NM_001407978.1:c.2026C>T NP_001394907.1:p.Gln676Ter nonsense NM_001407979.1:c.2023C>T NP_001394908.1:p.Gln675Ter nonsense NM_001407980.1:c.2023C>T NP_001394909.1:p.Gln675Ter nonsense NM_001407981.1:c.2023C>T NP_001394910.1:p.Gln675Ter nonsense NM_001407982.1:c.2023C>T NP_001394911.1:p.Gln675Ter nonsense NM_001407983.1:c.2023C>T NP_001394912.1:p.Gln675Ter nonsense NM_001407984.1:c.2023C>T NP_001394913.1:p.Gln675Ter nonsense NM_001407985.1:c.2023C>T NP_001394914.1:p.Gln675Ter nonsense NM_001407986.1:c.2023C>T NP_001394915.1:p.Gln675Ter nonsense NM_001407990.1:c.2023C>T NP_001394919.1:p.Gln675Ter nonsense NM_001407991.1:c.2023C>T NP_001394920.1:p.Gln675Ter nonsense NM_001407992.1:c.2023C>T NP_001394921.1:p.Gln675Ter nonsense NM_001407993.1:c.2023C>T NP_001394922.1:p.Gln675Ter nonsense NM_001408392.1:c.2020C>T NP_001395321.1:p.Gln674Ter nonsense NM_001408396.1:c.2020C>T NP_001395325.1:p.Gln674Ter nonsense NM_001408397.1:c.2020C>T NP_001395326.1:p.Gln674Ter nonsense NM_001408398.1:c.2020C>T NP_001395327.1:p.Gln674Ter nonsense NM_001408399.1:c.2020C>T NP_001395328.1:p.Gln674Ter nonsense NM_001408400.1:c.2020C>T NP_001395329.1:p.Gln674Ter nonsense NM_001408401.1:c.2020C>T NP_001395330.1:p.Gln674Ter nonsense NM_001408402.1:c.2020C>T NP_001395331.1:p.Gln674Ter nonsense NM_001408403.1:c.2020C>T NP_001395332.1:p.Gln674Ter nonsense NM_001408404.1:c.2020C>T NP_001395333.1:p.Gln674Ter nonsense NM_001408406.1:c.2017C>T NP_001395335.1:p.Gln673Ter nonsense NM_001408407.1:c.2017C>T NP_001395336.1:p.Gln673Ter nonsense NM_001408408.1:c.2017C>T NP_001395337.1:p.Gln673Ter nonsense NM_001408409.1:c.2014C>T NP_001395338.1:p.Gln672Ter nonsense NM_001408410.1:c.1951C>T NP_001395339.1:p.Gln651Ter nonsense NM_001408411.1:c.1948C>T NP_001395340.1:p.Gln650Ter nonsense NM_001408412.1:c.1945C>T NP_001395341.1:p.Gln649Ter nonsense NM_001408413.1:c.1945C>T NP_001395342.1:p.Gln649Ter nonsense NM_001408414.1:c.1945C>T NP_001395343.1:p.Gln649Ter nonsense NM_001408415.1:c.1945C>T NP_001395344.1:p.Gln649Ter nonsense NM_001408416.1:c.1945C>T NP_001395345.1:p.Gln649Ter nonsense NM_001408418.1:c.1909C>T NP_001395347.1:p.Gln637Ter nonsense NM_001408419.1:c.1909C>T NP_001395348.1:p.Gln637Ter nonsense NM_001408420.1:c.1909C>T NP_001395349.1:p.Gln637Ter nonsense NM_001408421.1:c.1906C>T NP_001395350.1:p.Gln636Ter nonsense NM_001408422.1:c.1906C>T NP_001395351.1:p.Gln636Ter nonsense NM_001408423.1:c.1906C>T NP_001395352.1:p.Gln636Ter nonsense NM_001408424.1:c.1906C>T NP_001395353.1:p.Gln636Ter nonsense NM_001408425.1:c.1903C>T NP_001395354.1:p.Gln635Ter nonsense NM_001408426.1:c.1903C>T NP_001395355.1:p.Gln635Ter nonsense NM_001408427.1:c.1903C>T NP_001395356.1:p.Gln635Ter nonsense NM_001408428.1:c.1903C>T NP_001395357.1:p.Gln635Ter nonsense NM_001408429.1:c.1903C>T NP_001395358.1:p.Gln635Ter nonsense NM_001408430.1:c.1903C>T NP_001395359.1:p.Gln635Ter nonsense NM_001408431.1:c.1903C>T NP_001395360.1:p.Gln635Ter nonsense NM_001408432.1:c.1900C>T NP_001395361.1:p.Gln634Ter nonsense NM_001408433.1:c.1900C>T NP_001395362.1:p.Gln634Ter nonsense NM_001408434.1:c.1900C>T NP_001395363.1:p.Gln634Ter nonsense NM_001408435.1:c.1900C>T NP_001395364.1:p.Gln634Ter nonsense NM_001408436.1:c.1900C>T NP_001395365.1:p.Gln634Ter nonsense NM_001408437.1:c.1900C>T NP_001395366.1:p.Gln634Ter nonsense NM_001408438.1:c.1900C>T NP_001395367.1:p.Gln634Ter nonsense NM_001408439.1:c.1900C>T NP_001395368.1:p.Gln634Ter nonsense NM_001408440.1:c.1900C>T NP_001395369.1:p.Gln634Ter nonsense NM_001408441.1:c.1900C>T NP_001395370.1:p.Gln634Ter nonsense NM_001408442.1:c.1900C>T NP_001395371.1:p.Gln634Ter nonsense NM_001408443.1:c.1900C>T NP_001395372.1:p.Gln634Ter nonsense NM_001408444.1:c.1900C>T NP_001395373.1:p.Gln634Ter nonsense NM_001408445.1:c.1897C>T NP_001395374.1:p.Gln633Ter nonsense NM_001408446.1:c.1897C>T NP_001395375.1:p.Gln633Ter nonsense NM_001408447.1:c.1897C>T NP_001395376.1:p.Gln633Ter nonsense NM_001408448.1:c.1897C>T NP_001395377.1:p.Gln633Ter nonsense NM_001408450.1:c.1897C>T NP_001395379.1:p.Gln633Ter nonsense NM_001408451.1:c.1891C>T NP_001395380.1:p.Gln631Ter nonsense NM_001408452.1:c.1885C>T NP_001395381.1:p.Gln629Ter nonsense NM_001408453.1:c.1885C>T NP_001395382.1:p.Gln629Ter nonsense NM_001408454.1:c.1885C>T NP_001395383.1:p.Gln629Ter nonsense NM_001408455.1:c.1885C>T NP_001395384.1:p.Gln629Ter nonsense NM_001408456.1:c.1885C>T NP_001395385.1:p.Gln629Ter nonsense NM_001408457.1:c.1885C>T NP_001395386.1:p.Gln629Ter nonsense NM_001408458.1:c.1882C>T NP_001395387.1:p.Gln628Ter nonsense NM_001408459.1:c.1882C>T NP_001395388.1:p.Gln628Ter nonsense NM_001408460.1:c.1882C>T NP_001395389.1:p.Gln628Ter nonsense NM_001408461.1:c.1882C>T NP_001395390.1:p.Gln628Ter nonsense NM_001408462.1:c.1882C>T NP_001395391.1:p.Gln628Ter nonsense NM_001408463.1:c.1882C>T NP_001395392.1:p.Gln628Ter nonsense NM_001408464.1:c.1882C>T NP_001395393.1:p.Gln628Ter nonsense NM_001408465.1:c.1882C>T NP_001395394.1:p.Gln628Ter nonsense NM_001408466.1:c.1882C>T NP_001395395.1:p.Gln628Ter nonsense NM_001408467.1:c.1882C>T NP_001395396.1:p.Gln628Ter nonsense NM_001408468.1:c.1879C>T NP_001395397.1:p.Gln627Ter nonsense NM_001408469.1:c.1879C>T NP_001395398.1:p.Gln627Ter nonsense NM_001408470.1:c.1879C>T NP_001395399.1:p.Gln627Ter nonsense NM_001408474.1:c.1825C>T NP_001395403.1:p.Gln609Ter nonsense NM_001408475.1:c.1822C>T NP_001395404.1:p.Gln608Ter nonsense NM_001408476.1:c.1822C>T NP_001395405.1:p.Gln608Ter nonsense NM_001408478.1:c.1816C>T NP_001395407.1:p.Gln606Ter nonsense NM_001408479.1:c.1816C>T NP_001395408.1:p.Gln606Ter nonsense NM_001408480.1:c.1816C>T NP_001395409.1:p.Gln606Ter nonsense NM_001408481.1:c.1813C>T NP_001395410.1:p.Gln605Ter nonsense NM_001408482.1:c.1813C>T NP_001395411.1:p.Gln605Ter nonsense NM_001408483.1:c.1813C>T NP_001395412.1:p.Gln605Ter nonsense NM_001408484.1:c.1813C>T NP_001395413.1:p.Gln605Ter nonsense NM_001408485.1:c.1813C>T NP_001395414.1:p.Gln605Ter nonsense NM_001408489.1:c.1813C>T NP_001395418.1:p.Gln605Ter nonsense NM_001408490.1:c.1813C>T NP_001395419.1:p.Gln605Ter nonsense NM_001408491.1:c.1813C>T NP_001395420.1:p.Gln605Ter nonsense NM_001408492.1:c.1810C>T NP_001395421.1:p.Gln604Ter nonsense NM_001408493.1:c.1810C>T NP_001395422.1:p.Gln604Ter nonsense NM_001408494.1:c.1786C>T NP_001395423.1:p.Gln596Ter nonsense NM_001408495.1:c.1780C>T NP_001395424.1:p.Gln594Ter nonsense NM_001408496.1:c.1762C>T NP_001395425.1:p.Gln588Ter nonsense NM_001408497.1:c.1762C>T NP_001395426.1:p.Gln588Ter nonsense NM_001408498.1:c.1762C>T NP_001395427.1:p.Gln588Ter nonsense NM_001408499.1:c.1762C>T NP_001395428.1:p.Gln588Ter nonsense NM_001408500.1:c.1762C>T NP_001395429.1:p.Gln588Ter nonsense NM_001408501.1:c.1762C>T NP_001395430.1:p.Gln588Ter nonsense NM_001408502.1:c.1759C>T NP_001395431.1:p.Gln587Ter nonsense NM_001408503.1:c.1759C>T NP_001395432.1:p.Gln587Ter nonsense NM_001408504.1:c.1759C>T NP_001395433.1:p.Gln587Ter nonsense NM_001408505.1:c.1756C>T NP_001395434.1:p.Gln586Ter nonsense NM_001408506.1:c.1699C>T NP_001395435.1:p.Gln567Ter nonsense NM_001408507.1:c.1696C>T NP_001395436.1:p.Gln566Ter nonsense NM_001408508.1:c.1687C>T NP_001395437.1:p.Gln563Ter nonsense NM_001408509.1:c.1684C>T NP_001395438.1:p.Gln562Ter nonsense NM_001408510.1:c.1645C>T NP_001395439.1:p.Gln549Ter nonsense NM_001408511.1:c.1642C>T NP_001395440.1:p.Gln548Ter nonsense NM_001408512.1:c.1522C>T NP_001395441.1:p.Gln508Ter nonsense NM_001408513.1:c.1495C>T NP_001395442.1:p.Gln499Ter nonsense NM_001408514.1:c.1099C>T NP_001395443.1:p.Gln367Ter nonsense NM_007297.4:c.5194C>T NP_009228.2:p.Gln1732Ter nonsense NM_007298.4:c.2023C>T NP_009229.2:p.Gln675Ter nonsense NM_007299.4:c.2021-1489C>T intron variant NM_007300.4:c.5398C>T NP_009231.2:p.Gln1800Ter nonsense NM_007304.2:c.2023C>T NP_009235.2:p.Gln675Ter nonsense NR_027676.2:n.5512C>T non-coding transcript variant NC_000017.11:g.43049192G>A NC_000017.10:g.41201209G>A NG_005905.2:g.168792C>T LRG_292:g.168792C>T LRG_292t1:c.5335C>T LRG_292p1:p.Gln1779Ter - Protein change
- Q1779*, Q1732*, Q675*, Q1800*, Q1482*, Q1708*, Q1738*, Q1752*, Q1759*, Q1799*, Q1801*, Q508*, Q548*, Q549*, Q566*, Q586*, Q587*, Q606*, Q627*, Q631*, Q633*, Q698*, Q1483*, Q1666*, Q1668*, Q1707*, Q1775*, Q1776*, Q1777*, Q563*, Q567*, Q605*, Q609*, Q629*, Q635*, Q637*, Q649*, Q651*, Q672*, Q1610*, Q1625*, Q1652*, Q1690*, Q1710*, Q1711*, Q1712*, Q1731*, Q1736*, Q1737*, Q1751*, Q1760*, Q1774*, Q367*, Q499*, Q594*, Q604*, Q608*, Q628*, Q634*, Q674*, Q697*, Q911*, Q1650*, Q1651*, Q1667*, Q1689*, Q1691*, Q1709*, Q1730*, Q1735*, Q1753*, Q1778*, Q562*, Q588*, Q596*, Q636*, Q650*, Q673*, Q676*, Q910*
- Other names
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5454C>T
- Canonical SPDI
- NC_000017.11:43049191:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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functionally_abnormal; Sequence Ontology [ SO:0002218]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5335C>T, a NONSENSE variant, produced a function score of -2.48, 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]
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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.
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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 |
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) |
reviewed by expert panel
|
Oct 18, 2016 | RCV000257216.15 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 27, 2022 | RCV000573772.12 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 30, 2022 | RCV000657615.10 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 8, 2023 | RCV001390967.16 |
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. |
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|---|---|---|---|---|---|
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Pathogenic
(Oct 18, 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: SCV000323865.2
First in ClinVar: Oct 22, 2016 Last updated: Feb 07, 2023 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
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Pathogenic
(Oct 14, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847910.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Gln1779X variant in BRCA1 has been reported in 2 siblings with early-onset breast cancer (Levanat 2012). It was absent from large population studies. This … (more)
The p.Gln1779X variant in BRCA1 has been reported in 2 siblings with early-onset breast cancer (Levanat 2012). It was absent from large population studies. This variant leads to a premature termination codon at position 1779, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC). In vitro functional studies support an impact on protein function (Findlay 2018). This variant was classified as Pathogenic on Oct 18, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID: 55540). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PM2, PS3_Moderate. (less)
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Pathogenic
(May 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000661070.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The c.5335C>T (p.Q1779*) alteration, located in exon 21 (coding exon 20) of the BRCA1 gene, consists of a C to T substitution at nucleotide position … (more)
The c.5335C>T (p.Q1779*) alteration, located in exon 21 (coding exon 20) of the BRCA1 gene, consists of a C to T substitution at nucleotide position 5335. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 1779. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple individuals diagnosed with early-onset breast cancer (Levanat, 2012). One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay, 2018). Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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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: SCV000326281.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Nov 30, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000779357.3
First in ClinVar: Jul 09, 2018 Last updated: Dec 17, 2022 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with breast cancer (Levanat et al., 2012); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (Findlay et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5454C>T; This variant is associated with the following publications: (PMID: 31589614, 29446198, 33087929, 29884841, 30209399, 32377563, 22366370) (less)
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Pathogenic
(Sep 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001592877.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln1779*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln1779*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 22366370). ClinVar contains an entry for this variant (Variation ID: 55540). For these reasons, this variant has been classified as Pathogenic. (less)
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not provided
(-)
|
no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
|
Brotman Baty Institute, University of Washington
Accession: SCV001238586.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.47967527520024
|
Comment:
Comment:
The p.Gln1779X variant in BRCA1 has been reported in 2 siblings with early-onset breast cancer (Levanat 2012). It was absent from large population studies. This variant leads to a premature termination codon at position 1779, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC). In vitro functional studies support an impact on protein function (Findlay 2018). This variant was classified as Pathogenic on Oct 18, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID: 55540). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PM2, PS3_Moderate.
Comment:
The c.5335C>T (p.Q1779*) alteration, located in exon 21 (coding exon 20) of the BRCA1 gene, consists of a C to T substitution at nucleotide position 5335. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 1779. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple individuals diagnosed with early-onset breast cancer (Levanat, 2012). One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay, 2018). Based on the available evidence, this alteration is classified as pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with breast cancer (Levanat et al., 2012); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (Findlay et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5454C>T; This variant is associated with the following publications: (PMID: 31589614, 29446198, 33087929, 29884841, 30209399, 32377563, 22366370)
Comment:
This sequence change creates a premature translational stop signal (p.Gln1779*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 22366370). ClinVar contains an entry for this variant (Variation ID: 55540). For these reasons, this variant has been classified as Pathogenic.
Germline Functional Evidence
| Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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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
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A brief description of the result of this method for this variant. |
Submitter
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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
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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: SCV001238586.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5335C>T, a NONSENSE variant, produced a function score of -2.48, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5335C>T, a NONSENSE variant, produced a function score of -2.48, 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 p.Gln1779X variant in BRCA1 has been reported in 2 siblings with early-onset breast cancer (Levanat 2012). It was absent from large population studies. This variant leads to a premature termination codon at position 1779, which is predicted to lead to a truncated or absent protein. Loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC). In vitro functional studies support an impact on protein function (Findlay 2018). This variant was classified as Pathogenic on Oct 18, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID: 55540). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PM2, PS3_Moderate.
Comment:
The c.5335C>T (p.Q1779*) alteration, located in exon 21 (coding exon 20) of the BRCA1 gene, consists of a C to T substitution at nucleotide position 5335. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 1779. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple individuals diagnosed with early-onset breast cancer (Levanat, 2012). One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay, 2018). Based on the available evidence, this alteration is classified as pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with breast cancer (Levanat et al., 2012); Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (Findlay et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5454C>T; This variant is associated with the following publications: (PMID: 31589614, 29446198, 33087929, 29884841, 30209399, 32377563, 22366370)
Comment:
This sequence change creates a premature translational stop signal (p.Gln1779*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 22366370). ClinVar contains an entry for this variant (Variation ID: 55540). For these reasons, this variant has been classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
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| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| Three novel BRCA1/BRCA2 mutations in breast/ovarian cancer families in Croatia. | Levanat S | Gene | 2012 | PMID: 22366370 |
| 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 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs397509267 ...
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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.