In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55231). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1527 of the BRCA1 protein (p.Glu1527Lys).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4579G>A (p.Glu1527Lys)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(3)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4579G>A (p.Glu1527Lys)
Variation ID: 55231 Accession: VCV000055231.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074427 (GRCh38) [ NCBI UCSC ] 17: 41226444 (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 17, 2024 Dec 2, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4579G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1527Lys missense NM_001407571.1:c.4366G>A NP_001394500.1:p.Glu1456Lys missense NM_001407581.1:c.4645G>A NP_001394510.1:p.Glu1549Lys missense NM_001407582.1:c.4645G>A NP_001394511.1:p.Glu1549Lys missense NM_001407583.1:c.4642G>A NP_001394512.1:p.Glu1548Lys missense NM_001407585.1:c.4642G>A NP_001394514.1:p.Glu1548Lys missense NM_001407587.1:c.4642G>A NP_001394516.1:p.Glu1548Lys missense NM_001407590.1:c.4639G>A NP_001394519.1:p.Glu1547Lys missense NM_001407591.1:c.4639G>A NP_001394520.1:p.Glu1547Lys missense NM_001407593.1:c.4579G>A NP_001394522.1:p.Glu1527Lys missense NM_001407594.1:c.4579G>A NP_001394523.1:p.Glu1527Lys missense NM_001407596.1:c.4579G>A NP_001394525.1:p.Glu1527Lys missense NM_001407597.1:c.4579G>A NP_001394526.1:p.Glu1527Lys missense NM_001407598.1:c.4579G>A NP_001394527.1:p.Glu1527Lys missense NM_001407602.1:c.4579G>A NP_001394531.1:p.Glu1527Lys missense NM_001407603.1:c.4579G>A NP_001394532.1:p.Glu1527Lys missense NM_001407605.1:c.4579G>A NP_001394534.1:p.Glu1527Lys missense NM_001407610.1:c.4576G>A NP_001394539.1:p.Glu1526Lys missense NM_001407611.1:c.4576G>A NP_001394540.1:p.Glu1526Lys missense NM_001407612.1:c.4576G>A NP_001394541.1:p.Glu1526Lys missense NM_001407613.1:c.4576G>A NP_001394542.1:p.Glu1526Lys missense NM_001407614.1:c.4576G>A NP_001394543.1:p.Glu1526Lys missense NM_001407615.1:c.4576G>A NP_001394544.1:p.Glu1526Lys missense NM_001407616.1:c.4576G>A NP_001394545.1:p.Glu1526Lys missense NM_001407617.1:c.4576G>A NP_001394546.1:p.Glu1526Lys missense NM_001407618.1:c.4576G>A NP_001394547.1:p.Glu1526Lys missense NM_001407619.1:c.4576G>A NP_001394548.1:p.Glu1526Lys missense NM_001407620.1:c.4576G>A NP_001394549.1:p.Glu1526Lys missense NM_001407621.1:c.4576G>A NP_001394550.1:p.Glu1526Lys missense NM_001407622.1:c.4576G>A NP_001394551.1:p.Glu1526Lys missense NM_001407623.1:c.4576G>A NP_001394552.1:p.Glu1526Lys missense NM_001407624.1:c.4576G>A NP_001394553.1:p.Glu1526Lys missense NM_001407625.1:c.4576G>A NP_001394554.1:p.Glu1526Lys missense NM_001407626.1:c.4576G>A NP_001394555.1:p.Glu1526Lys missense NM_001407627.1:c.4573G>A NP_001394556.1:p.Glu1525Lys missense NM_001407628.1:c.4573G>A NP_001394557.1:p.Glu1525Lys missense NM_001407629.1:c.4573G>A NP_001394558.1:p.Glu1525Lys missense NM_001407630.1:c.4573G>A NP_001394559.1:p.Glu1525Lys missense NM_001407631.1:c.4573G>A NP_001394560.1:p.Glu1525Lys missense NM_001407632.1:c.4573G>A NP_001394561.1:p.Glu1525Lys missense NM_001407633.1:c.4573G>A NP_001394562.1:p.Glu1525Lys missense NM_001407634.1:c.4573G>A NP_001394563.1:p.Glu1525Lys missense NM_001407635.1:c.4573G>A NP_001394564.1:p.Glu1525Lys missense NM_001407636.1:c.4573G>A NP_001394565.1:p.Glu1525Lys missense NM_001407637.1:c.4573G>A NP_001394566.1:p.Glu1525Lys missense NM_001407638.1:c.4573G>A NP_001394567.1:p.Glu1525Lys missense NM_001407639.1:c.4573G>A NP_001394568.1:p.Glu1525Lys missense NM_001407640.1:c.4573G>A NP_001394569.1:p.Glu1525Lys missense NM_001407641.1:c.4573G>A NP_001394570.1:p.Glu1525Lys missense NM_001407642.1:c.4573G>A NP_001394571.1:p.Glu1525Lys missense NM_001407644.1:c.4570G>A NP_001394573.1:p.Glu1524Lys missense NM_001407645.1:c.4570G>A NP_001394574.1:p.Glu1524Lys missense NM_001407646.1:c.4567G>A NP_001394575.1:p.Glu1523Lys missense NM_001407647.1:c.4564G>A NP_001394576.1:p.Glu1522Lys missense NM_001407648.1:c.4522G>A NP_001394577.1:p.Glu1508Lys missense NM_001407649.1:c.4519G>A NP_001394578.1:p.Glu1507Lys missense NM_001407652.1:c.4579G>A NP_001394581.1:p.Glu1527Lys missense NM_001407653.1:c.4501G>A NP_001394582.1:p.Glu1501Lys missense NM_001407654.1:c.4501G>A NP_001394583.1:p.Glu1501Lys missense NM_001407655.1:c.4501G>A NP_001394584.1:p.Glu1501Lys missense NM_001407656.1:c.4498G>A NP_001394585.1:p.Glu1500Lys missense NM_001407657.1:c.4498G>A NP_001394586.1:p.Glu1500Lys missense NM_001407658.1:c.4498G>A NP_001394587.1:p.Glu1500Lys missense NM_001407659.1:c.4495G>A NP_001394588.1:p.Glu1499Lys missense NM_001407660.1:c.4495G>A NP_001394589.1:p.Glu1499Lys missense NM_001407661.1:c.4495G>A NP_001394590.1:p.Glu1499Lys missense NM_001407662.1:c.4495G>A NP_001394591.1:p.Glu1499Lys missense NM_001407663.1:c.4495G>A NP_001394592.1:p.Glu1499Lys missense NM_001407664.1:c.4456G>A NP_001394593.1:p.Glu1486Lys missense NM_001407665.1:c.4456G>A NP_001394594.1:p.Glu1486Lys missense NM_001407666.1:c.4456G>A NP_001394595.1:p.Glu1486Lys missense NM_001407667.1:c.4456G>A NP_001394596.1:p.Glu1486Lys missense NM_001407668.1:c.4456G>A NP_001394597.1:p.Glu1486Lys missense NM_001407669.1:c.4456G>A NP_001394598.1:p.Glu1486Lys missense NM_001407670.1:c.4453G>A NP_001394599.1:p.Glu1485Lys missense NM_001407671.1:c.4453G>A NP_001394600.1:p.Glu1485Lys missense NM_001407672.1:c.4453G>A NP_001394601.1:p.Glu1485Lys missense NM_001407673.1:c.4453G>A NP_001394602.1:p.Glu1485Lys missense NM_001407674.1:c.4453G>A NP_001394603.1:p.Glu1485Lys missense NM_001407675.1:c.4453G>A NP_001394604.1:p.Glu1485Lys missense NM_001407676.1:c.4453G>A NP_001394605.1:p.Glu1485Lys missense NM_001407677.1:c.4453G>A NP_001394606.1:p.Glu1485Lys missense NM_001407678.1:c.4453G>A NP_001394607.1:p.Glu1485Lys missense NM_001407679.1:c.4453G>A NP_001394608.1:p.Glu1485Lys missense NM_001407680.1:c.4453G>A NP_001394609.1:p.Glu1485Lys missense NM_001407681.1:c.4450G>A NP_001394610.1:p.Glu1484Lys missense NM_001407682.1:c.4450G>A NP_001394611.1:p.Glu1484Lys missense NM_001407683.1:c.4450G>A NP_001394612.1:p.Glu1484Lys missense NM_001407684.1:c.4579G>A NP_001394613.1:p.Glu1527Lys missense NM_001407685.1:c.4450G>A NP_001394614.1:p.Glu1484Lys missense NM_001407686.1:c.4450G>A NP_001394615.1:p.Glu1484Lys missense NM_001407687.1:c.4450G>A NP_001394616.1:p.Glu1484Lys missense NM_001407688.1:c.4450G>A NP_001394617.1:p.Glu1484Lys missense NM_001407689.1:c.4450G>A NP_001394618.1:p.Glu1484Lys missense NM_001407690.1:c.4447G>A NP_001394619.1:p.Glu1483Lys missense NM_001407691.1:c.4447G>A NP_001394620.1:p.Glu1483Lys missense NM_001407692.1:c.4438G>A NP_001394621.1:p.Glu1480Lys missense NM_001407694.1:c.4438G>A NP_001394623.1:p.Glu1480Lys missense NM_001407695.1:c.4438G>A NP_001394624.1:p.Glu1480Lys missense NM_001407696.1:c.4438G>A NP_001394625.1:p.Glu1480Lys missense NM_001407697.1:c.4438G>A NP_001394626.1:p.Glu1480Lys missense NM_001407698.1:c.4438G>A NP_001394627.1:p.Glu1480Lys missense NM_001407724.1:c.4438G>A NP_001394653.1:p.Glu1480Lys missense NM_001407725.1:c.4438G>A NP_001394654.1:p.Glu1480Lys missense NM_001407726.1:c.4438G>A NP_001394655.1:p.Glu1480Lys missense NM_001407727.1:c.4438G>A NP_001394656.1:p.Glu1480Lys missense NM_001407728.1:c.4438G>A NP_001394657.1:p.Glu1480Lys missense NM_001407729.1:c.4438G>A NP_001394658.1:p.Glu1480Lys missense NM_001407730.1:c.4438G>A NP_001394659.1:p.Glu1480Lys missense NM_001407731.1:c.4438G>A NP_001394660.1:p.Glu1480Lys missense NM_001407732.1:c.4435G>A NP_001394661.1:p.Glu1479Lys missense NM_001407733.1:c.4435G>A NP_001394662.1:p.Glu1479Lys missense NM_001407734.1:c.4435G>A NP_001394663.1:p.Glu1479Lys missense NM_001407735.1:c.4435G>A NP_001394664.1:p.Glu1479Lys missense NM_001407736.1:c.4435G>A NP_001394665.1:p.Glu1479Lys missense NM_001407737.1:c.4435G>A NP_001394666.1:p.Glu1479Lys missense NM_001407738.1:c.4435G>A NP_001394667.1:p.Glu1479Lys missense NM_001407739.1:c.4435G>A NP_001394668.1:p.Glu1479Lys missense NM_001407740.1:c.4435G>A NP_001394669.1:p.Glu1479Lys missense NM_001407741.1:c.4435G>A NP_001394670.1:p.Glu1479Lys missense NM_001407742.1:c.4435G>A NP_001394671.1:p.Glu1479Lys missense NM_001407743.1:c.4435G>A NP_001394672.1:p.Glu1479Lys missense NM_001407744.1:c.4435G>A NP_001394673.1:p.Glu1479Lys missense NM_001407745.1:c.4435G>A NP_001394674.1:p.Glu1479Lys missense NM_001407746.1:c.4435G>A NP_001394675.1:p.Glu1479Lys missense NM_001407747.1:c.4435G>A NP_001394676.1:p.Glu1479Lys missense NM_001407748.1:c.4435G>A NP_001394677.1:p.Glu1479Lys missense NM_001407749.1:c.4435G>A NP_001394678.1:p.Glu1479Lys missense NM_001407750.1:c.4435G>A NP_001394679.1:p.Glu1479Lys missense NM_001407751.1:c.4435G>A NP_001394680.1:p.Glu1479Lys missense NM_001407752.1:c.4435G>A NP_001394681.1:p.Glu1479Lys missense NM_001407838.1:c.4432G>A NP_001394767.1:p.Glu1478Lys missense NM_001407839.1:c.4432G>A NP_001394768.1:p.Glu1478Lys missense NM_001407841.1:c.4432G>A NP_001394770.1:p.Glu1478Lys missense NM_001407842.1:c.4432G>A NP_001394771.1:p.Glu1478Lys missense NM_001407843.1:c.4432G>A NP_001394772.1:p.Glu1478Lys missense NM_001407844.1:c.4432G>A NP_001394773.1:p.Glu1478Lys missense NM_001407845.1:c.4432G>A NP_001394774.1:p.Glu1478Lys missense NM_001407846.1:c.4432G>A NP_001394775.1:p.Glu1478Lys missense NM_001407847.1:c.4432G>A NP_001394776.1:p.Glu1478Lys missense NM_001407848.1:c.4432G>A NP_001394777.1:p.Glu1478Lys missense NM_001407849.1:c.4432G>A NP_001394778.1:p.Glu1478Lys missense NM_001407850.1:c.4432G>A NP_001394779.1:p.Glu1478Lys missense NM_001407851.1:c.4432G>A NP_001394780.1:p.Glu1478Lys missense NM_001407852.1:c.4432G>A NP_001394781.1:p.Glu1478Lys missense NM_001407853.1:c.4432G>A NP_001394782.1:p.Glu1478Lys missense NM_001407854.1:c.4579G>A NP_001394783.1:p.Glu1527Lys missense NM_001407858.1:c.4576G>A NP_001394787.1:p.Glu1526Lys missense NM_001407859.1:c.4576G>A NP_001394788.1:p.Glu1526Lys missense NM_001407860.1:c.4576G>A NP_001394789.1:p.Glu1526Lys missense NM_001407861.1:c.4573G>A NP_001394790.1:p.Glu1525Lys missense NM_001407862.1:c.4378G>A NP_001394791.1:p.Glu1460Lys missense NM_001407863.1:c.4453G>A NP_001394792.1:p.Glu1485Lys missense NM_001407874.1:c.4372G>A NP_001394803.1:p.Glu1458Lys missense NM_001407875.1:c.4372G>A NP_001394804.1:p.Glu1458Lys missense NM_001407879.1:c.4369G>A NP_001394808.1:p.Glu1457Lys missense NM_001407881.1:c.4369G>A NP_001394810.1:p.Glu1457Lys missense NM_001407882.1:c.4369G>A NP_001394811.1:p.Glu1457Lys missense NM_001407884.1:c.4369G>A NP_001394813.1:p.Glu1457Lys missense NM_001407885.1:c.4369G>A NP_001394814.1:p.Glu1457Lys missense NM_001407886.1:c.4369G>A NP_001394815.1:p.Glu1457Lys missense NM_001407887.1:c.4369G>A NP_001394816.1:p.Glu1457Lys missense NM_001407889.1:c.4369G>A NP_001394818.1:p.Glu1457Lys missense NM_001407894.1:c.4366G>A NP_001394823.1:p.Glu1456Lys missense NM_001407895.1:c.4366G>A NP_001394824.1:p.Glu1456Lys missense NM_001407896.1:c.4366G>A NP_001394825.1:p.Glu1456Lys missense NM_001407897.1:c.4366G>A NP_001394826.1:p.Glu1456Lys missense NM_001407898.1:c.4366G>A NP_001394827.1:p.Glu1456Lys missense NM_001407899.1:c.4366G>A NP_001394828.1:p.Glu1456Lys missense NM_001407900.1:c.4366G>A NP_001394829.1:p.Glu1456Lys missense NM_001407902.1:c.4366G>A NP_001394831.1:p.Glu1456Lys missense NM_001407904.1:c.4366G>A NP_001394833.1:p.Glu1456Lys missense NM_001407906.1:c.4366G>A NP_001394835.1:p.Glu1456Lys missense NM_001407907.1:c.4366G>A NP_001394836.1:p.Glu1456Lys missense NM_001407908.1:c.4366G>A NP_001394837.1:p.Glu1456Lys missense NM_001407909.1:c.4366G>A NP_001394838.1:p.Glu1456Lys missense NM_001407910.1:c.4366G>A NP_001394839.1:p.Glu1456Lys missense NM_001407915.1:c.4363G>A NP_001394844.1:p.Glu1455Lys missense NM_001407916.1:c.4363G>A NP_001394845.1:p.Glu1455Lys missense NM_001407917.1:c.4363G>A NP_001394846.1:p.Glu1455Lys missense NM_001407918.1:c.4363G>A NP_001394847.1:p.Glu1455Lys missense NM_001407919.1:c.4456G>A NP_001394848.1:p.Glu1486Lys missense NM_001407920.1:c.4315G>A NP_001394849.1:p.Glu1439Lys missense NM_001407921.1:c.4315G>A NP_001394850.1:p.Glu1439Lys missense NM_001407922.1:c.4315G>A NP_001394851.1:p.Glu1439Lys missense NM_001407923.1:c.4315G>A NP_001394852.1:p.Glu1439Lys missense NM_001407924.1:c.4315G>A NP_001394853.1:p.Glu1439Lys missense NM_001407925.1:c.4315G>A NP_001394854.1:p.Glu1439Lys missense NM_001407926.1:c.4315G>A NP_001394855.1:p.Glu1439Lys missense NM_001407927.1:c.4312G>A NP_001394856.1:p.Glu1438Lys missense NM_001407928.1:c.4312G>A NP_001394857.1:p.Glu1438Lys missense NM_001407929.1:c.4312G>A NP_001394858.1:p.Glu1438Lys missense NM_001407930.1:c.4312G>A NP_001394859.1:p.Glu1438Lys missense NM_001407931.1:c.4312G>A NP_001394860.1:p.Glu1438Lys missense NM_001407932.1:c.4312G>A NP_001394861.1:p.Glu1438Lys missense NM_001407933.1:c.4312G>A NP_001394862.1:p.Glu1438Lys missense NM_001407934.1:c.4309G>A NP_001394863.1:p.Glu1437Lys missense NM_001407935.1:c.4309G>A NP_001394864.1:p.Glu1437Lys missense NM_001407936.1:c.4309G>A NP_001394865.1:p.Glu1437Lys missense NM_001407937.1:c.4456G>A NP_001394866.1:p.Glu1486Lys missense NM_001407938.1:c.4456G>A NP_001394867.1:p.Glu1486Lys missense NM_001407939.1:c.4453G>A NP_001394868.1:p.Glu1485Lys missense NM_001407940.1:c.4453G>A NP_001394869.1:p.Glu1485Lys missense NM_001407941.1:c.4450G>A NP_001394870.1:p.Glu1484Lys missense NM_001407942.1:c.4438G>A NP_001394871.1:p.Glu1480Lys missense NM_001407943.1:c.4435G>A NP_001394872.1:p.Glu1479Lys missense NM_001407944.1:c.4435G>A NP_001394873.1:p.Glu1479Lys missense NM_001407945.1:c.4435G>A NP_001394874.1:p.Glu1479Lys missense NM_001407946.1:c.4246G>A NP_001394875.1:p.Glu1416Lys missense NM_001407947.1:c.4246G>A NP_001394876.1:p.Glu1416Lys missense NM_001407948.1:c.4246G>A NP_001394877.1:p.Glu1416Lys missense NM_001407949.1:c.4246G>A NP_001394878.1:p.Glu1416Lys missense NM_001407950.1:c.4243G>A NP_001394879.1:p.Glu1415Lys missense NM_001407951.1:c.4243G>A NP_001394880.1:p.Glu1415Lys missense NM_001407952.1:c.4243G>A NP_001394881.1:p.Glu1415Lys missense NM_001407953.1:c.4243G>A NP_001394882.1:p.Glu1415Lys missense NM_001407954.1:c.4243G>A NP_001394883.1:p.Glu1415Lys missense NM_001407955.1:c.4243G>A NP_001394884.1:p.Glu1415Lys missense NM_001407956.1:c.4240G>A NP_001394885.1:p.Glu1414Lys missense NM_001407957.1:c.4240G>A NP_001394886.1:p.Glu1414Lys missense NM_001407958.1:c.4240G>A NP_001394887.1:p.Glu1414Lys missense NM_001407959.1:c.4198G>A NP_001394888.1:p.Glu1400Lys missense NM_001407960.1:c.4195G>A NP_001394889.1:p.Glu1399Lys missense NM_001407962.1:c.4195G>A NP_001394891.1:p.Glu1399Lys missense NM_001407963.1:c.4192G>A NP_001394892.1:p.Glu1398Lys missense NM_001407965.1:c.4072G>A NP_001394894.1:p.Glu1358Lys missense NM_001407966.1:c.3691G>A NP_001394895.1:p.Glu1231Lys missense NM_001407967.1:c.3688G>A NP_001394896.1:p.Glu1230Lys missense NM_001407968.1:c.1975G>A NP_001394897.1:p.Glu659Lys missense NM_001407969.1:c.1972G>A NP_001394898.1:p.Glu658Lys missense NM_001407970.1:c.1336G>A NP_001394899.1:p.Glu446Lys missense NM_001407971.1:c.1336G>A NP_001394900.1:p.Glu446Lys missense NM_001407972.1:c.1333G>A NP_001394901.1:p.Glu445Lys missense NM_001407973.1:c.1270G>A NP_001394902.1:p.Glu424Lys missense NM_001407974.1:c.1270G>A NP_001394903.1:p.Glu424Lys missense NM_001407975.1:c.1270G>A NP_001394904.1:p.Glu424Lys missense NM_001407976.1:c.1270G>A NP_001394905.1:p.Glu424Lys missense NM_001407977.1:c.1270G>A NP_001394906.1:p.Glu424Lys missense NM_001407978.1:c.1270G>A NP_001394907.1:p.Glu424Lys missense NM_001407979.1:c.1267G>A NP_001394908.1:p.Glu423Lys missense NM_001407980.1:c.1267G>A NP_001394909.1:p.Glu423Lys missense NM_001407981.1:c.1267G>A NP_001394910.1:p.Glu423Lys missense NM_001407982.1:c.1267G>A NP_001394911.1:p.Glu423Lys missense NM_001407983.1:c.1267G>A NP_001394912.1:p.Glu423Lys missense NM_001407984.1:c.1267G>A NP_001394913.1:p.Glu423Lys missense NM_001407985.1:c.1267G>A NP_001394914.1:p.Glu423Lys missense NM_001407986.1:c.1267G>A NP_001394915.1:p.Glu423Lys missense NM_001407990.1:c.1267G>A NP_001394919.1:p.Glu423Lys missense NM_001407991.1:c.1267G>A NP_001394920.1:p.Glu423Lys missense NM_001407992.1:c.1267G>A NP_001394921.1:p.Glu423Lys missense NM_001407993.1:c.1267G>A NP_001394922.1:p.Glu423Lys missense NM_001408392.1:c.1264G>A NP_001395321.1:p.Glu422Lys missense NM_001408396.1:c.1264G>A NP_001395325.1:p.Glu422Lys missense NM_001408397.1:c.1264G>A NP_001395326.1:p.Glu422Lys missense NM_001408398.1:c.1264G>A NP_001395327.1:p.Glu422Lys missense NM_001408399.1:c.1264G>A NP_001395328.1:p.Glu422Lys missense NM_001408400.1:c.1264G>A NP_001395329.1:p.Glu422Lys missense NM_001408401.1:c.1264G>A NP_001395330.1:p.Glu422Lys missense NM_001408402.1:c.1264G>A NP_001395331.1:p.Glu422Lys missense NM_001408403.1:c.1264G>A NP_001395332.1:p.Glu422Lys missense NM_001408404.1:c.1264G>A NP_001395333.1:p.Glu422Lys missense NM_001408406.1:c.1261G>A NP_001395335.1:p.Glu421Lys missense NM_001408407.1:c.1261G>A NP_001395336.1:p.Glu421Lys missense NM_001408408.1:c.1261G>A NP_001395337.1:p.Glu421Lys missense NM_001408409.1:c.1258G>A NP_001395338.1:p.Glu420Lys missense NM_001408410.1:c.1195G>A NP_001395339.1:p.Glu399Lys missense NM_001408411.1:c.1192G>A NP_001395340.1:p.Glu398Lys missense NM_001408412.1:c.1189G>A NP_001395341.1:p.Glu397Lys missense NM_001408413.1:c.1189G>A NP_001395342.1:p.Glu397Lys missense NM_001408414.1:c.1189G>A NP_001395343.1:p.Glu397Lys missense NM_001408415.1:c.1189G>A NP_001395344.1:p.Glu397Lys missense NM_001408416.1:c.1189G>A NP_001395345.1:p.Glu397Lys missense NM_001408418.1:c.1153G>A NP_001395347.1:p.Glu385Lys missense NM_001408419.1:c.1153G>A NP_001395348.1:p.Glu385Lys missense NM_001408420.1:c.1153G>A NP_001395349.1:p.Glu385Lys missense NM_001408421.1:c.1150G>A NP_001395350.1:p.Glu384Lys missense NM_001408422.1:c.1150G>A NP_001395351.1:p.Glu384Lys missense NM_001408423.1:c.1150G>A NP_001395352.1:p.Glu384Lys missense NM_001408424.1:c.1150G>A NP_001395353.1:p.Glu384Lys missense NM_001408425.1:c.1147G>A NP_001395354.1:p.Glu383Lys missense NM_001408426.1:c.1147G>A NP_001395355.1:p.Glu383Lys missense NM_001408427.1:c.1147G>A NP_001395356.1:p.Glu383Lys missense NM_001408428.1:c.1147G>A NP_001395357.1:p.Glu383Lys missense NM_001408429.1:c.1147G>A NP_001395358.1:p.Glu383Lys missense NM_001408430.1:c.1147G>A NP_001395359.1:p.Glu383Lys missense NM_001408431.1:c.1147G>A NP_001395360.1:p.Glu383Lys missense NM_001408432.1:c.1144G>A NP_001395361.1:p.Glu382Lys missense NM_001408433.1:c.1144G>A NP_001395362.1:p.Glu382Lys missense NM_001408434.1:c.1144G>A NP_001395363.1:p.Glu382Lys missense NM_001408435.1:c.1144G>A NP_001395364.1:p.Glu382Lys missense NM_001408436.1:c.1144G>A NP_001395365.1:p.Glu382Lys missense NM_001408437.1:c.1144G>A NP_001395366.1:p.Glu382Lys missense NM_001408438.1:c.1144G>A NP_001395367.1:p.Glu382Lys missense NM_001408439.1:c.1144G>A NP_001395368.1:p.Glu382Lys missense NM_001408440.1:c.1144G>A NP_001395369.1:p.Glu382Lys missense NM_001408441.1:c.1144G>A NP_001395370.1:p.Glu382Lys missense NM_001408442.1:c.1144G>A NP_001395371.1:p.Glu382Lys missense NM_001408443.1:c.1144G>A NP_001395372.1:p.Glu382Lys missense NM_001408444.1:c.1144G>A NP_001395373.1:p.Glu382Lys missense NM_001408445.1:c.1141G>A NP_001395374.1:p.Glu381Lys missense NM_001408446.1:c.1141G>A NP_001395375.1:p.Glu381Lys missense NM_001408447.1:c.1141G>A NP_001395376.1:p.Glu381Lys missense NM_001408448.1:c.1141G>A NP_001395377.1:p.Glu381Lys missense NM_001408450.1:c.1141G>A NP_001395379.1:p.Glu381Lys missense NM_001408451.1:c.1135G>A NP_001395380.1:p.Glu379Lys missense NM_001408452.1:c.1129G>A NP_001395381.1:p.Glu377Lys missense NM_001408453.1:c.1129G>A NP_001395382.1:p.Glu377Lys missense NM_001408454.1:c.1129G>A NP_001395383.1:p.Glu377Lys missense NM_001408455.1:c.1129G>A NP_001395384.1:p.Glu377Lys missense NM_001408456.1:c.1129G>A NP_001395385.1:p.Glu377Lys missense NM_001408457.1:c.1129G>A NP_001395386.1:p.Glu377Lys missense NM_001408458.1:c.1126G>A NP_001395387.1:p.Glu376Lys missense NM_001408459.1:c.1126G>A NP_001395388.1:p.Glu376Lys missense NM_001408460.1:c.1126G>A NP_001395389.1:p.Glu376Lys missense NM_001408461.1:c.1126G>A NP_001395390.1:p.Glu376Lys missense NM_001408462.1:c.1126G>A NP_001395391.1:p.Glu376Lys missense NM_001408463.1:c.1126G>A NP_001395392.1:p.Glu376Lys missense NM_001408464.1:c.1126G>A NP_001395393.1:p.Glu376Lys missense NM_001408465.1:c.1126G>A NP_001395394.1:p.Glu376Lys missense NM_001408466.1:c.1126G>A NP_001395395.1:p.Glu376Lys missense NM_001408467.1:c.1126G>A NP_001395396.1:p.Glu376Lys missense NM_001408468.1:c.1123G>A NP_001395397.1:p.Glu375Lys missense NM_001408469.1:c.1123G>A NP_001395398.1:p.Glu375Lys missense NM_001408470.1:c.1123G>A NP_001395399.1:p.Glu375Lys missense NM_001408472.1:c.1267G>A NP_001395401.1:p.Glu423Lys missense NM_001408473.1:c.1264G>A NP_001395402.1:p.Glu422Lys missense NM_001408474.1:c.1069G>A NP_001395403.1:p.Glu357Lys missense NM_001408475.1:c.1066G>A NP_001395404.1:p.Glu356Lys missense NM_001408476.1:c.1066G>A NP_001395405.1:p.Glu356Lys missense NM_001408478.1:c.1060G>A NP_001395407.1:p.Glu354Lys missense NM_001408479.1:c.1060G>A NP_001395408.1:p.Glu354Lys missense NM_001408480.1:c.1060G>A NP_001395409.1:p.Glu354Lys missense NM_001408481.1:c.1057G>A NP_001395410.1:p.Glu353Lys missense NM_001408482.1:c.1057G>A NP_001395411.1:p.Glu353Lys missense NM_001408483.1:c.1057G>A NP_001395412.1:p.Glu353Lys missense NM_001408484.1:c.1057G>A NP_001395413.1:p.Glu353Lys missense NM_001408485.1:c.1057G>A NP_001395414.1:p.Glu353Lys missense NM_001408489.1:c.1057G>A NP_001395418.1:p.Glu353Lys missense NM_001408490.1:c.1057G>A NP_001395419.1:p.Glu353Lys missense NM_001408491.1:c.1057G>A NP_001395420.1:p.Glu353Lys missense NM_001408492.1:c.1054G>A NP_001395421.1:p.Glu352Lys missense NM_001408493.1:c.1054G>A NP_001395422.1:p.Glu352Lys missense NM_001408494.1:c.1030G>A NP_001395423.1:p.Glu344Lys missense NM_001408495.1:c.1024G>A NP_001395424.1:p.Glu342Lys missense NM_001408496.1:c.1006G>A NP_001395425.1:p.Glu336Lys missense NM_001408497.1:c.1006G>A NP_001395426.1:p.Glu336Lys missense NM_001408498.1:c.1006G>A NP_001395427.1:p.Glu336Lys missense NM_001408499.1:c.1006G>A NP_001395428.1:p.Glu336Lys missense NM_001408500.1:c.1006G>A NP_001395429.1:p.Glu336Lys missense NM_001408501.1:c.1006G>A NP_001395430.1:p.Glu336Lys missense NM_001408502.1:c.1003G>A NP_001395431.1:p.Glu335Lys missense NM_001408503.1:c.1003G>A NP_001395432.1:p.Glu335Lys missense NM_001408504.1:c.1003G>A NP_001395433.1:p.Glu335Lys missense NM_001408505.1:c.1000G>A NP_001395434.1:p.Glu334Lys missense NM_001408506.1:c.943G>A NP_001395435.1:p.Glu315Lys missense NM_001408507.1:c.940G>A NP_001395436.1:p.Glu314Lys missense NM_001408508.1:c.931G>A NP_001395437.1:p.Glu311Lys missense NM_001408509.1:c.928G>A NP_001395438.1:p.Glu310Lys missense NM_001408510.1:c.889G>A NP_001395439.1:p.Glu297Lys missense NM_001408511.1:c.886G>A NP_001395440.1:p.Glu296Lys missense NM_001408512.1:c.766G>A NP_001395441.1:p.Glu256Lys missense NM_007297.4:c.4438G>A NP_009228.2:p.Glu1480Lys missense NM_007298.4:c.1267G>A NP_009229.2:p.Glu423Lys missense NM_007299.4:c.1267G>A NP_009230.2:p.Glu423Lys missense NM_007300.4:c.4642G>A NP_009231.2:p.Glu1548Lys missense NM_007304.2:c.1267G>A NP_009235.2:p.Glu423Lys missense NR_027676.2:n.4756G>A non-coding transcript variant NC_000017.11:g.43074427C>T NC_000017.10:g.41226444C>T NG_005905.2:g.143557G>A LRG_292:g.143557G>A LRG_292t1:c.4579G>A LRG_292p1:p.Glu1527Lys U14680.1:n.4698G>A - Protein change
- E1527K, E423K, E1548K, E1480K, E1230K, E1400K, E1415K, E1437K, E1438K, E1457K, E1483K, E1500K, E1507K, E1522K, E256K, E314K, E334K, E354K, E356K, E379K, E382K, E383K, E420K, E445K, E1358K, E1399K, E1479K, E1485K, E1499K, E1508K, E1525K, E1547K, E1549K, E296K, E352K, E375K, E376K, E377K, E397K, E424K, E446K, E658K, E1231K, E1414K, E1455K, E1458K, E1460K, E1478K, E1484K, E1486K, E1523K, E1524K, E297K, E310K, E311K, E315K, E335K, E336K, E342K, E399K, E422K, E1398K, E1416K, E1439K, E1456K, E1501K, E1526K, E344K, E353K, E357K, E381K, E384K, E385K, E398K, E421K, E659K
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074426:C:T
-
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. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, single submitter
|
Dec 2, 2023 | RCV000112359.4 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
May 12, 2023 | RCV003644889.2 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Dec 02, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005058312.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
|
Uncertain significance
(May 12, 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: SCV004516838.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant … (more)
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55231). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1527 of the BRCA1 protein (p.Glu1527Lys). (less)
|
|
|
Uncertain significance
(Nov 25, 2004)
|
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: SCV000145121.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ireland, Canada
|
Comment:
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:
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55231). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1527 of the BRCA1 protein (p.Glu1527Lys).
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs80357237 ...
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 Oct 08, 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.