This missense variant replaces glutamic acid with aspartic acid at codon 1559 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant is reported in an individual affected with ovarian cancer (PMID: 21965345). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4677G>C (p.Glu1559Asp)
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.
(2)
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
2
criteria provided, multiple submitters, no conflicts
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.4677G>C (p.Glu1559Asp)
Variation ID: 141610 Accession: VCV000141610.7
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43071237 (GRCh38) [ NCBI UCSC ] 17: 41223254 (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 Mar 24, 2015 May 1, 2024 Feb 5, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4677G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1559Asp missense NM_001407571.1:c.4464G>C NP_001394500.1:p.Glu1488Asp missense NM_001407581.1:c.4743G>C NP_001394510.1:p.Glu1581Asp missense NM_001407582.1:c.4743G>C NP_001394511.1:p.Glu1581Asp missense NM_001407583.1:c.4740G>C NP_001394512.1:p.Glu1580Asp missense NM_001407585.1:c.4740G>C NP_001394514.1:p.Glu1580Asp missense NM_001407587.1:c.4740G>C NP_001394516.1:p.Glu1580Asp missense NM_001407590.1:c.4737G>C NP_001394519.1:p.Glu1579Asp missense NM_001407591.1:c.4737G>C NP_001394520.1:p.Glu1579Asp missense NM_001407593.1:c.4677G>C NP_001394522.1:p.Glu1559Asp missense NM_001407594.1:c.4677G>C NP_001394523.1:p.Glu1559Asp missense NM_001407596.1:c.4677G>C NP_001394525.1:p.Glu1559Asp missense NM_001407597.1:c.4677G>C NP_001394526.1:p.Glu1559Asp missense NM_001407598.1:c.4677G>C NP_001394527.1:p.Glu1559Asp missense NM_001407602.1:c.4677G>C NP_001394531.1:p.Glu1559Asp missense NM_001407603.1:c.4677G>C NP_001394532.1:p.Glu1559Asp missense NM_001407605.1:c.4677G>C NP_001394534.1:p.Glu1559Asp missense NM_001407610.1:c.4674G>C NP_001394539.1:p.Glu1558Asp missense NM_001407611.1:c.4674G>C NP_001394540.1:p.Glu1558Asp missense NM_001407612.1:c.4674G>C NP_001394541.1:p.Glu1558Asp missense NM_001407613.1:c.4674G>C NP_001394542.1:p.Glu1558Asp missense NM_001407614.1:c.4674G>C NP_001394543.1:p.Glu1558Asp missense NM_001407615.1:c.4674G>C NP_001394544.1:p.Glu1558Asp missense NM_001407616.1:c.4674G>C NP_001394545.1:p.Glu1558Asp missense NM_001407617.1:c.4674G>C NP_001394546.1:p.Glu1558Asp missense NM_001407618.1:c.4674G>C NP_001394547.1:p.Glu1558Asp missense NM_001407619.1:c.4674G>C NP_001394548.1:p.Glu1558Asp missense NM_001407620.1:c.4674G>C NP_001394549.1:p.Glu1558Asp missense NM_001407621.1:c.4674G>C NP_001394550.1:p.Glu1558Asp missense NM_001407622.1:c.4674G>C NP_001394551.1:p.Glu1558Asp missense NM_001407623.1:c.4674G>C NP_001394552.1:p.Glu1558Asp missense NM_001407624.1:c.4674G>C NP_001394553.1:p.Glu1558Asp missense NM_001407625.1:c.4674G>C NP_001394554.1:p.Glu1558Asp missense NM_001407626.1:c.4674G>C NP_001394555.1:p.Glu1558Asp missense NM_001407627.1:c.4671G>C NP_001394556.1:p.Glu1557Asp missense NM_001407628.1:c.4671G>C NP_001394557.1:p.Glu1557Asp missense NM_001407629.1:c.4671G>C NP_001394558.1:p.Glu1557Asp missense NM_001407630.1:c.4671G>C NP_001394559.1:p.Glu1557Asp missense NM_001407631.1:c.4671G>C NP_001394560.1:p.Glu1557Asp missense NM_001407632.1:c.4671G>C NP_001394561.1:p.Glu1557Asp missense NM_001407633.1:c.4671G>C NP_001394562.1:p.Glu1557Asp missense NM_001407634.1:c.4671G>C NP_001394563.1:p.Glu1557Asp missense NM_001407635.1:c.4671G>C NP_001394564.1:p.Glu1557Asp missense NM_001407636.1:c.4671G>C NP_001394565.1:p.Glu1557Asp missense NM_001407637.1:c.4671G>C NP_001394566.1:p.Glu1557Asp missense NM_001407638.1:c.4671G>C NP_001394567.1:p.Glu1557Asp missense NM_001407639.1:c.4671G>C NP_001394568.1:p.Glu1557Asp missense NM_001407640.1:c.4671G>C NP_001394569.1:p.Glu1557Asp missense NM_001407641.1:c.4671G>C NP_001394570.1:p.Glu1557Asp missense NM_001407642.1:c.4671G>C NP_001394571.1:p.Glu1557Asp missense NM_001407644.1:c.4668G>C NP_001394573.1:p.Glu1556Asp missense NM_001407645.1:c.4668G>C NP_001394574.1:p.Glu1556Asp missense NM_001407646.1:c.4665G>C NP_001394575.1:p.Glu1555Asp missense NM_001407647.1:c.4662G>C NP_001394576.1:p.Glu1554Asp missense NM_001407648.1:c.4620G>C NP_001394577.1:p.Glu1540Asp missense NM_001407649.1:c.4617G>C NP_001394578.1:p.Glu1539Asp missense NM_001407652.1:c.4677G>C NP_001394581.1:p.Glu1559Asp missense NM_001407653.1:c.4599G>C NP_001394582.1:p.Glu1533Asp missense NM_001407654.1:c.4599G>C NP_001394583.1:p.Glu1533Asp missense NM_001407655.1:c.4599G>C NP_001394584.1:p.Glu1533Asp missense NM_001407656.1:c.4596G>C NP_001394585.1:p.Glu1532Asp missense NM_001407657.1:c.4596G>C NP_001394586.1:p.Glu1532Asp missense NM_001407658.1:c.4596G>C NP_001394587.1:p.Glu1532Asp missense NM_001407659.1:c.4593G>C NP_001394588.1:p.Glu1531Asp missense NM_001407660.1:c.4593G>C NP_001394589.1:p.Glu1531Asp missense NM_001407661.1:c.4593G>C NP_001394590.1:p.Glu1531Asp missense NM_001407662.1:c.4593G>C NP_001394591.1:p.Glu1531Asp missense NM_001407663.1:c.4593G>C NP_001394592.1:p.Glu1531Asp missense NM_001407664.1:c.4554G>C NP_001394593.1:p.Glu1518Asp missense NM_001407665.1:c.4554G>C NP_001394594.1:p.Glu1518Asp missense NM_001407666.1:c.4554G>C NP_001394595.1:p.Glu1518Asp missense NM_001407667.1:c.4554G>C NP_001394596.1:p.Glu1518Asp missense NM_001407668.1:c.4554G>C NP_001394597.1:p.Glu1518Asp missense NM_001407669.1:c.4554G>C NP_001394598.1:p.Glu1518Asp missense NM_001407670.1:c.4551G>C NP_001394599.1:p.Glu1517Asp missense NM_001407671.1:c.4551G>C NP_001394600.1:p.Glu1517Asp missense NM_001407672.1:c.4551G>C NP_001394601.1:p.Glu1517Asp missense NM_001407673.1:c.4551G>C NP_001394602.1:p.Glu1517Asp missense NM_001407674.1:c.4551G>C NP_001394603.1:p.Glu1517Asp missense NM_001407675.1:c.4551G>C NP_001394604.1:p.Glu1517Asp missense NM_001407676.1:c.4551G>C NP_001394605.1:p.Glu1517Asp missense NM_001407677.1:c.4551G>C NP_001394606.1:p.Glu1517Asp missense NM_001407678.1:c.4551G>C NP_001394607.1:p.Glu1517Asp missense NM_001407679.1:c.4551G>C NP_001394608.1:p.Glu1517Asp missense NM_001407680.1:c.4551G>C NP_001394609.1:p.Glu1517Asp missense NM_001407681.1:c.4548G>C NP_001394610.1:p.Glu1516Asp missense NM_001407682.1:c.4548G>C NP_001394611.1:p.Glu1516Asp missense NM_001407683.1:c.4548G>C NP_001394612.1:p.Glu1516Asp missense NM_001407684.1:c.4677G>C NP_001394613.1:p.Glu1559Asp missense NM_001407685.1:c.4548G>C NP_001394614.1:p.Glu1516Asp missense NM_001407686.1:c.4548G>C NP_001394615.1:p.Glu1516Asp missense NM_001407687.1:c.4548G>C NP_001394616.1:p.Glu1516Asp missense NM_001407688.1:c.4548G>C NP_001394617.1:p.Glu1516Asp missense NM_001407689.1:c.4548G>C NP_001394618.1:p.Glu1516Asp missense NM_001407690.1:c.4545G>C NP_001394619.1:p.Glu1515Asp missense NM_001407691.1:c.4545G>C NP_001394620.1:p.Glu1515Asp missense NM_001407692.1:c.4536G>C NP_001394621.1:p.Glu1512Asp missense NM_001407694.1:c.4536G>C NP_001394623.1:p.Glu1512Asp missense NM_001407695.1:c.4536G>C NP_001394624.1:p.Glu1512Asp missense NM_001407696.1:c.4536G>C NP_001394625.1:p.Glu1512Asp missense NM_001407697.1:c.4536G>C NP_001394626.1:p.Glu1512Asp missense NM_001407698.1:c.4536G>C NP_001394627.1:p.Glu1512Asp missense NM_001407724.1:c.4536G>C NP_001394653.1:p.Glu1512Asp missense NM_001407725.1:c.4536G>C NP_001394654.1:p.Glu1512Asp missense NM_001407726.1:c.4536G>C NP_001394655.1:p.Glu1512Asp missense NM_001407727.1:c.4536G>C NP_001394656.1:p.Glu1512Asp missense NM_001407728.1:c.4536G>C NP_001394657.1:p.Glu1512Asp missense NM_001407729.1:c.4536G>C NP_001394658.1:p.Glu1512Asp missense NM_001407730.1:c.4536G>C NP_001394659.1:p.Glu1512Asp missense NM_001407731.1:c.4536G>C NP_001394660.1:p.Glu1512Asp missense NM_001407732.1:c.4533G>C NP_001394661.1:p.Glu1511Asp missense NM_001407733.1:c.4533G>C NP_001394662.1:p.Glu1511Asp missense NM_001407734.1:c.4533G>C NP_001394663.1:p.Glu1511Asp missense NM_001407735.1:c.4533G>C NP_001394664.1:p.Glu1511Asp missense NM_001407736.1:c.4533G>C NP_001394665.1:p.Glu1511Asp missense NM_001407737.1:c.4533G>C NP_001394666.1:p.Glu1511Asp missense NM_001407738.1:c.4533G>C NP_001394667.1:p.Glu1511Asp missense NM_001407739.1:c.4533G>C NP_001394668.1:p.Glu1511Asp missense NM_001407740.1:c.4533G>C NP_001394669.1:p.Glu1511Asp missense NM_001407741.1:c.4533G>C NP_001394670.1:p.Glu1511Asp missense NM_001407742.1:c.4533G>C NP_001394671.1:p.Glu1511Asp missense NM_001407743.1:c.4533G>C NP_001394672.1:p.Glu1511Asp missense NM_001407744.1:c.4533G>C NP_001394673.1:p.Glu1511Asp missense NM_001407745.1:c.4533G>C NP_001394674.1:p.Glu1511Asp missense NM_001407746.1:c.4533G>C NP_001394675.1:p.Glu1511Asp missense NM_001407747.1:c.4533G>C NP_001394676.1:p.Glu1511Asp missense NM_001407748.1:c.4533G>C NP_001394677.1:p.Glu1511Asp missense NM_001407749.1:c.4533G>C NP_001394678.1:p.Glu1511Asp missense NM_001407750.1:c.4533G>C NP_001394679.1:p.Glu1511Asp missense NM_001407751.1:c.4533G>C NP_001394680.1:p.Glu1511Asp missense NM_001407752.1:c.4533G>C NP_001394681.1:p.Glu1511Asp missense NM_001407838.1:c.4530G>C NP_001394767.1:p.Glu1510Asp missense NM_001407839.1:c.4530G>C NP_001394768.1:p.Glu1510Asp missense NM_001407841.1:c.4530G>C NP_001394770.1:p.Glu1510Asp missense NM_001407842.1:c.4530G>C NP_001394771.1:p.Glu1510Asp missense NM_001407843.1:c.4530G>C NP_001394772.1:p.Glu1510Asp missense NM_001407844.1:c.4530G>C NP_001394773.1:p.Glu1510Asp missense NM_001407845.1:c.4530G>C NP_001394774.1:p.Glu1510Asp missense NM_001407846.1:c.4530G>C NP_001394775.1:p.Glu1510Asp missense NM_001407847.1:c.4530G>C NP_001394776.1:p.Glu1510Asp missense NM_001407848.1:c.4530G>C NP_001394777.1:p.Glu1510Asp missense NM_001407849.1:c.4530G>C NP_001394778.1:p.Glu1510Asp missense NM_001407850.1:c.4530G>C NP_001394779.1:p.Glu1510Asp missense NM_001407851.1:c.4530G>C NP_001394780.1:p.Glu1510Asp missense NM_001407852.1:c.4530G>C NP_001394781.1:p.Glu1510Asp missense NM_001407853.1:c.4530G>C NP_001394782.1:p.Glu1510Asp missense NM_001407854.1:c.4677G>C NP_001394783.1:p.Glu1559Asp missense NM_001407858.1:c.4674G>C NP_001394787.1:p.Glu1558Asp missense NM_001407859.1:c.4674G>C NP_001394788.1:p.Glu1558Asp missense NM_001407860.1:c.4674G>C NP_001394789.1:p.Glu1558Asp missense NM_001407861.1:c.4671G>C NP_001394790.1:p.Glu1557Asp missense NM_001407862.1:c.4476G>C NP_001394791.1:p.Glu1492Asp missense NM_001407863.1:c.4551G>C NP_001394792.1:p.Glu1517Asp missense NM_001407874.1:c.4470G>C NP_001394803.1:p.Glu1490Asp missense NM_001407875.1:c.4470G>C NP_001394804.1:p.Glu1490Asp missense NM_001407879.1:c.4467G>C NP_001394808.1:p.Glu1489Asp missense NM_001407881.1:c.4467G>C NP_001394810.1:p.Glu1489Asp missense NM_001407882.1:c.4467G>C NP_001394811.1:p.Glu1489Asp missense NM_001407884.1:c.4467G>C NP_001394813.1:p.Glu1489Asp missense NM_001407885.1:c.4467G>C NP_001394814.1:p.Glu1489Asp missense NM_001407886.1:c.4467G>C NP_001394815.1:p.Glu1489Asp missense NM_001407887.1:c.4467G>C NP_001394816.1:p.Glu1489Asp missense NM_001407889.1:c.4467G>C NP_001394818.1:p.Glu1489Asp missense NM_001407894.1:c.4464G>C NP_001394823.1:p.Glu1488Asp missense NM_001407895.1:c.4464G>C NP_001394824.1:p.Glu1488Asp missense NM_001407896.1:c.4464G>C NP_001394825.1:p.Glu1488Asp missense NM_001407897.1:c.4464G>C NP_001394826.1:p.Glu1488Asp missense NM_001407898.1:c.4464G>C NP_001394827.1:p.Glu1488Asp missense NM_001407899.1:c.4464G>C NP_001394828.1:p.Glu1488Asp missense NM_001407900.1:c.4464G>C NP_001394829.1:p.Glu1488Asp missense NM_001407902.1:c.4464G>C NP_001394831.1:p.Glu1488Asp missense NM_001407904.1:c.4464G>C NP_001394833.1:p.Glu1488Asp missense NM_001407906.1:c.4464G>C NP_001394835.1:p.Glu1488Asp missense NM_001407907.1:c.4464G>C NP_001394836.1:p.Glu1488Asp missense NM_001407908.1:c.4464G>C NP_001394837.1:p.Glu1488Asp missense NM_001407909.1:c.4464G>C NP_001394838.1:p.Glu1488Asp missense NM_001407910.1:c.4464G>C NP_001394839.1:p.Glu1488Asp missense NM_001407915.1:c.4461G>C NP_001394844.1:p.Glu1487Asp missense NM_001407916.1:c.4461G>C NP_001394845.1:p.Glu1487Asp missense NM_001407917.1:c.4461G>C NP_001394846.1:p.Glu1487Asp missense NM_001407918.1:c.4461G>C NP_001394847.1:p.Glu1487Asp missense NM_001407919.1:c.4554G>C NP_001394848.1:p.Glu1518Asp missense NM_001407920.1:c.4413G>C NP_001394849.1:p.Glu1471Asp missense NM_001407921.1:c.4413G>C NP_001394850.1:p.Glu1471Asp missense NM_001407922.1:c.4413G>C NP_001394851.1:p.Glu1471Asp missense NM_001407923.1:c.4413G>C NP_001394852.1:p.Glu1471Asp missense NM_001407924.1:c.4413G>C NP_001394853.1:p.Glu1471Asp missense NM_001407925.1:c.4413G>C NP_001394854.1:p.Glu1471Asp missense NM_001407926.1:c.4413G>C NP_001394855.1:p.Glu1471Asp missense NM_001407927.1:c.4410G>C NP_001394856.1:p.Glu1470Asp missense NM_001407928.1:c.4410G>C NP_001394857.1:p.Glu1470Asp missense NM_001407929.1:c.4410G>C NP_001394858.1:p.Glu1470Asp missense NM_001407930.1:c.4410G>C NP_001394859.1:p.Glu1470Asp missense NM_001407931.1:c.4410G>C NP_001394860.1:p.Glu1470Asp missense NM_001407932.1:c.4410G>C NP_001394861.1:p.Glu1470Asp missense NM_001407933.1:c.4410G>C NP_001394862.1:p.Glu1470Asp missense NM_001407934.1:c.4407G>C NP_001394863.1:p.Glu1469Asp missense NM_001407935.1:c.4407G>C NP_001394864.1:p.Glu1469Asp missense NM_001407936.1:c.4407G>C NP_001394865.1:p.Glu1469Asp missense NM_001407937.1:c.4554G>C NP_001394866.1:p.Glu1518Asp missense NM_001407938.1:c.4554G>C NP_001394867.1:p.Glu1518Asp missense NM_001407939.1:c.4551G>C NP_001394868.1:p.Glu1517Asp missense NM_001407940.1:c.4551G>C NP_001394869.1:p.Glu1517Asp missense NM_001407941.1:c.4548G>C NP_001394870.1:p.Glu1516Asp missense NM_001407942.1:c.4536G>C NP_001394871.1:p.Glu1512Asp missense NM_001407943.1:c.4533G>C NP_001394872.1:p.Glu1511Asp missense NM_001407944.1:c.4533G>C NP_001394873.1:p.Glu1511Asp missense NM_001407945.1:c.4533G>C NP_001394874.1:p.Glu1511Asp missense NM_001407946.1:c.4344G>C NP_001394875.1:p.Glu1448Asp missense NM_001407947.1:c.4344G>C NP_001394876.1:p.Glu1448Asp missense NM_001407948.1:c.4344G>C NP_001394877.1:p.Glu1448Asp missense NM_001407949.1:c.4344G>C NP_001394878.1:p.Glu1448Asp missense NM_001407950.1:c.4341G>C NP_001394879.1:p.Glu1447Asp missense NM_001407951.1:c.4341G>C NP_001394880.1:p.Glu1447Asp missense NM_001407952.1:c.4341G>C NP_001394881.1:p.Glu1447Asp missense NM_001407953.1:c.4341G>C NP_001394882.1:p.Glu1447Asp missense NM_001407954.1:c.4341G>C NP_001394883.1:p.Glu1447Asp missense NM_001407955.1:c.4341G>C NP_001394884.1:p.Glu1447Asp missense NM_001407956.1:c.4338G>C NP_001394885.1:p.Glu1446Asp missense NM_001407957.1:c.4338G>C NP_001394886.1:p.Glu1446Asp missense NM_001407958.1:c.4338G>C NP_001394887.1:p.Glu1446Asp missense NM_001407959.1:c.4296G>C NP_001394888.1:p.Glu1432Asp missense NM_001407960.1:c.4293G>C NP_001394889.1:p.Glu1431Asp missense NM_001407962.1:c.4293G>C NP_001394891.1:p.Glu1431Asp missense NM_001407963.1:c.4290G>C NP_001394892.1:p.Glu1430Asp missense NM_001407964.1:c.4215G>C NP_001394893.1:p.Glu1405Asp missense NM_001407965.1:c.4170G>C NP_001394894.1:p.Glu1390Asp missense NM_001407966.1:c.3789G>C NP_001394895.1:p.Glu1263Asp missense NM_001407967.1:c.3786G>C NP_001394896.1:p.Glu1262Asp missense NM_001407968.1:c.2073G>C NP_001394897.1:p.Glu691Asp missense NM_001407969.1:c.2070G>C NP_001394898.1:p.Glu690Asp missense NM_001407970.1:c.1434G>C NP_001394899.1:p.Glu478Asp missense NM_001407971.1:c.1434G>C NP_001394900.1:p.Glu478Asp missense NM_001407972.1:c.1431G>C NP_001394901.1:p.Glu477Asp missense NM_001407973.1:c.1368G>C NP_001394902.1:p.Glu456Asp missense NM_001407974.1:c.1368G>C NP_001394903.1:p.Glu456Asp missense NM_001407975.1:c.1368G>C NP_001394904.1:p.Glu456Asp missense NM_001407976.1:c.1368G>C NP_001394905.1:p.Glu456Asp missense NM_001407977.1:c.1368G>C NP_001394906.1:p.Glu456Asp missense NM_001407978.1:c.1368G>C NP_001394907.1:p.Glu456Asp missense NM_001407979.1:c.1365G>C NP_001394908.1:p.Glu455Asp missense NM_001407980.1:c.1365G>C NP_001394909.1:p.Glu455Asp missense NM_001407981.1:c.1365G>C NP_001394910.1:p.Glu455Asp missense NM_001407982.1:c.1365G>C NP_001394911.1:p.Glu455Asp missense NM_001407983.1:c.1365G>C NP_001394912.1:p.Glu455Asp missense NM_001407984.1:c.1365G>C NP_001394913.1:p.Glu455Asp missense NM_001407985.1:c.1365G>C NP_001394914.1:p.Glu455Asp missense NM_001407986.1:c.1365G>C NP_001394915.1:p.Glu455Asp missense NM_001407990.1:c.1365G>C NP_001394919.1:p.Glu455Asp missense NM_001407991.1:c.1365G>C NP_001394920.1:p.Glu455Asp missense NM_001407992.1:c.1365G>C NP_001394921.1:p.Glu455Asp missense NM_001407993.1:c.1365G>C NP_001394922.1:p.Glu455Asp missense NM_001408392.1:c.1362G>C NP_001395321.1:p.Glu454Asp missense NM_001408396.1:c.1362G>C NP_001395325.1:p.Glu454Asp missense NM_001408397.1:c.1362G>C NP_001395326.1:p.Glu454Asp missense NM_001408398.1:c.1362G>C NP_001395327.1:p.Glu454Asp missense NM_001408399.1:c.1362G>C NP_001395328.1:p.Glu454Asp missense NM_001408400.1:c.1362G>C NP_001395329.1:p.Glu454Asp missense NM_001408401.1:c.1362G>C NP_001395330.1:p.Glu454Asp missense NM_001408402.1:c.1362G>C NP_001395331.1:p.Glu454Asp missense NM_001408403.1:c.1362G>C NP_001395332.1:p.Glu454Asp missense NM_001408404.1:c.1362G>C NP_001395333.1:p.Glu454Asp missense NM_001408406.1:c.1359G>C NP_001395335.1:p.Glu453Asp missense NM_001408407.1:c.1359G>C NP_001395336.1:p.Glu453Asp missense NM_001408408.1:c.1359G>C NP_001395337.1:p.Glu453Asp missense NM_001408409.1:c.1356G>C NP_001395338.1:p.Glu452Asp missense NM_001408410.1:c.1293G>C NP_001395339.1:p.Glu431Asp missense NM_001408411.1:c.1290G>C NP_001395340.1:p.Glu430Asp missense NM_001408412.1:c.1287G>C NP_001395341.1:p.Glu429Asp missense NM_001408413.1:c.1287G>C NP_001395342.1:p.Glu429Asp missense NM_001408414.1:c.1287G>C NP_001395343.1:p.Glu429Asp missense NM_001408415.1:c.1287G>C NP_001395344.1:p.Glu429Asp missense NM_001408416.1:c.1287G>C NP_001395345.1:p.Glu429Asp missense NM_001408418.1:c.1251G>C NP_001395347.1:p.Glu417Asp missense NM_001408419.1:c.1251G>C NP_001395348.1:p.Glu417Asp missense NM_001408420.1:c.1251G>C NP_001395349.1:p.Glu417Asp missense NM_001408421.1:c.1248G>C NP_001395350.1:p.Glu416Asp missense NM_001408422.1:c.1248G>C NP_001395351.1:p.Glu416Asp missense NM_001408423.1:c.1248G>C NP_001395352.1:p.Glu416Asp missense NM_001408424.1:c.1248G>C NP_001395353.1:p.Glu416Asp missense NM_001408425.1:c.1245G>C NP_001395354.1:p.Glu415Asp missense NM_001408426.1:c.1245G>C NP_001395355.1:p.Glu415Asp missense NM_001408427.1:c.1245G>C NP_001395356.1:p.Glu415Asp missense NM_001408428.1:c.1245G>C NP_001395357.1:p.Glu415Asp missense NM_001408429.1:c.1245G>C NP_001395358.1:p.Glu415Asp missense NM_001408430.1:c.1245G>C NP_001395359.1:p.Glu415Asp missense NM_001408431.1:c.1245G>C NP_001395360.1:p.Glu415Asp missense NM_001408432.1:c.1242G>C NP_001395361.1:p.Glu414Asp missense NM_001408433.1:c.1242G>C NP_001395362.1:p.Glu414Asp missense NM_001408434.1:c.1242G>C NP_001395363.1:p.Glu414Asp missense NM_001408435.1:c.1242G>C NP_001395364.1:p.Glu414Asp missense NM_001408436.1:c.1242G>C NP_001395365.1:p.Glu414Asp missense NM_001408437.1:c.1242G>C NP_001395366.1:p.Glu414Asp missense NM_001408438.1:c.1242G>C NP_001395367.1:p.Glu414Asp missense NM_001408439.1:c.1242G>C NP_001395368.1:p.Glu414Asp missense NM_001408440.1:c.1242G>C NP_001395369.1:p.Glu414Asp missense NM_001408441.1:c.1242G>C NP_001395370.1:p.Glu414Asp missense NM_001408442.1:c.1242G>C NP_001395371.1:p.Glu414Asp missense NM_001408443.1:c.1242G>C NP_001395372.1:p.Glu414Asp missense NM_001408444.1:c.1242G>C NP_001395373.1:p.Glu414Asp missense NM_001408445.1:c.1239G>C NP_001395374.1:p.Glu413Asp missense NM_001408446.1:c.1239G>C NP_001395375.1:p.Glu413Asp missense NM_001408447.1:c.1239G>C NP_001395376.1:p.Glu413Asp missense NM_001408448.1:c.1239G>C NP_001395377.1:p.Glu413Asp missense NM_001408450.1:c.1239G>C NP_001395379.1:p.Glu413Asp missense NM_001408451.1:c.1233G>C NP_001395380.1:p.Glu411Asp missense NM_001408452.1:c.1227G>C NP_001395381.1:p.Glu409Asp missense NM_001408453.1:c.1227G>C NP_001395382.1:p.Glu409Asp missense NM_001408454.1:c.1227G>C NP_001395383.1:p.Glu409Asp missense NM_001408455.1:c.1227G>C NP_001395384.1:p.Glu409Asp missense NM_001408456.1:c.1227G>C NP_001395385.1:p.Glu409Asp missense NM_001408457.1:c.1227G>C NP_001395386.1:p.Glu409Asp missense NM_001408458.1:c.1224G>C NP_001395387.1:p.Glu408Asp missense NM_001408459.1:c.1224G>C NP_001395388.1:p.Glu408Asp missense NM_001408460.1:c.1224G>C NP_001395389.1:p.Glu408Asp missense NM_001408461.1:c.1224G>C NP_001395390.1:p.Glu408Asp missense NM_001408462.1:c.1224G>C NP_001395391.1:p.Glu408Asp missense NM_001408463.1:c.1224G>C NP_001395392.1:p.Glu408Asp missense NM_001408464.1:c.1224G>C NP_001395393.1:p.Glu408Asp missense NM_001408465.1:c.1224G>C NP_001395394.1:p.Glu408Asp missense NM_001408466.1:c.1224G>C NP_001395395.1:p.Glu408Asp missense NM_001408467.1:c.1224G>C NP_001395396.1:p.Glu408Asp missense NM_001408468.1:c.1221G>C NP_001395397.1:p.Glu407Asp missense NM_001408469.1:c.1221G>C NP_001395398.1:p.Glu407Asp missense NM_001408470.1:c.1221G>C NP_001395399.1:p.Glu407Asp missense NM_001408472.1:c.1365G>C NP_001395401.1:p.Glu455Asp missense NM_001408473.1:c.1362G>C NP_001395402.1:p.Glu454Asp missense NM_001408474.1:c.1167G>C NP_001395403.1:p.Glu389Asp missense NM_001408475.1:c.1164G>C NP_001395404.1:p.Glu388Asp missense NM_001408476.1:c.1164G>C NP_001395405.1:p.Glu388Asp missense NM_001408478.1:c.1158G>C NP_001395407.1:p.Glu386Asp missense NM_001408479.1:c.1158G>C NP_001395408.1:p.Glu386Asp missense NM_001408480.1:c.1158G>C NP_001395409.1:p.Glu386Asp missense NM_001408481.1:c.1155G>C NP_001395410.1:p.Glu385Asp missense NM_001408482.1:c.1155G>C NP_001395411.1:p.Glu385Asp missense NM_001408483.1:c.1155G>C NP_001395412.1:p.Glu385Asp missense NM_001408484.1:c.1155G>C NP_001395413.1:p.Glu385Asp missense NM_001408485.1:c.1155G>C NP_001395414.1:p.Glu385Asp missense NM_001408489.1:c.1155G>C NP_001395418.1:p.Glu385Asp missense NM_001408490.1:c.1155G>C NP_001395419.1:p.Glu385Asp missense NM_001408491.1:c.1155G>C NP_001395420.1:p.Glu385Asp missense NM_001408492.1:c.1152G>C NP_001395421.1:p.Glu384Asp missense NM_001408493.1:c.1152G>C NP_001395422.1:p.Glu384Asp missense NM_001408494.1:c.1128G>C NP_001395423.1:p.Glu376Asp missense NM_001408495.1:c.1122G>C NP_001395424.1:p.Glu374Asp missense NM_001408496.1:c.1104G>C NP_001395425.1:p.Glu368Asp missense NM_001408497.1:c.1104G>C NP_001395426.1:p.Glu368Asp missense NM_001408498.1:c.1104G>C NP_001395427.1:p.Glu368Asp missense NM_001408499.1:c.1104G>C NP_001395428.1:p.Glu368Asp missense NM_001408500.1:c.1104G>C NP_001395429.1:p.Glu368Asp missense NM_001408501.1:c.1104G>C NP_001395430.1:p.Glu368Asp missense NM_001408502.1:c.1101G>C NP_001395431.1:p.Glu367Asp missense NM_001408503.1:c.1101G>C NP_001395432.1:p.Glu367Asp missense NM_001408504.1:c.1101G>C NP_001395433.1:p.Glu367Asp missense NM_001408505.1:c.1098G>C NP_001395434.1:p.Glu366Asp missense NM_001408506.1:c.1041G>C NP_001395435.1:p.Glu347Asp missense NM_001408507.1:c.1038G>C NP_001395436.1:p.Glu346Asp missense NM_001408508.1:c.1029G>C NP_001395437.1:p.Glu343Asp missense NM_001408509.1:c.1026G>C NP_001395438.1:p.Glu342Asp missense NM_001408510.1:c.987G>C NP_001395439.1:p.Glu329Asp missense NM_001408511.1:c.984G>C NP_001395440.1:p.Glu328Asp missense NM_001408512.1:c.864G>C NP_001395441.1:p.Glu288Asp missense NM_001408513.1:c.837G>C NP_001395442.1:p.Glu279Asp missense NM_007297.4:c.4536G>C NP_009228.2:p.Glu1512Asp missense NM_007298.4:c.1365G>C NP_009229.2:p.Glu455Asp missense NM_007299.4:c.1365G>C NP_009230.2:p.Glu455Asp missense NM_007300.4:c.4740G>C NP_009231.2:p.Glu1580Asp missense NM_007304.2:c.1365G>C NP_009235.2:p.Glu455Asp missense NR_027676.2:n.4854G>C non-coding transcript variant NC_000017.11:g.43071237C>G NC_000017.10:g.41223254C>G NG_005905.2:g.146747G>C LRG_292:g.146747G>C LRG_292t1:c.4677G>C LRG_292p1:p.Glu1559Asp - Protein change
- E1559D, E1512D, E455D, E1580D, E1431D, E1448D, E1518D, E1540D, E1555D, E1556D, E1557D, E1581D, E279D, E343D, E368D, E374D, E385D, E388D, E415D, E416D, E431D, E1263D, E1390D, E1446D, E1515D, E1532D, E1533D, E1539D, E1554D, E1558D, E288D, E367D, E384D, E407D, E408D, E409D, E430D, E452D, E456D, E477D, E691D, E1262D, E1430D, E1447D, E1487D, E1490D, E1492D, E1510D, E1517D, E1579D, E328D, E346D, E366D, E376D, E389D, E411D, E414D, E417D, E429D, E453D, E690D, E1405D, E1432D, E1469D, E1470D, E1471D, E1488D, E1489D, E1511D, E1516D, E1531D, E329D, E342D, E347D, E386D, E413D, E454D, E478D
- Other names
- -
- Canonical SPDI
- NC_000017.11:43071236:C:G
-
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 (1) |
criteria provided, single submitter
|
May 6, 2021 | RCV000130202.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 5, 2024 | RCV003997555.2 |
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
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004834599.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant replaces glutamic acid with aspartic acid at codon 1559 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this … (more)
This missense variant replaces glutamic acid with aspartic acid at codon 1559 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant is reported in an individual affected with ovarian cancer (PMID: 21965345). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
|
|
|
Uncertain significance
(May 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185039.7
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.E1559D variant (also known as c.4677G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide … (more)
The p.E1559D variant (also known as c.4677G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide position 4677. The glutamic acid at codon 1559 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Akbari MR et al. J Med Genet, 2011 Nov;48:783-6). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The p.E1559D variant (also known as c.4677G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide position 4677. The glutamic acid at codon 1559 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Akbari MR et al. J Med Genet, 2011 Nov;48:783-6). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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:
This missense variant replaces glutamic acid with aspartic acid at codon 1559 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant is reported in an individual affected with ovarian cancer (PMID: 21965345). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
The p.E1559D variant (also known as c.4677G>C), located in coding exon 14 of the BRCA1 gene, results from a G to C substitution at nucleotide position 4677. The glutamic acid at codon 1559 is replaced by aspartic acid, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Akbari MR et al. J Med Genet, 2011 Nov;48:783-6). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Clinical impact of unclassified variants of the BRCA1 and BRCA2 genes. | Akbari MR | Journal of medical genetics | 2011 | PMID: 21965345 |
Text-mined citations for rs587781876 ...
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Record last updated Oct 08, 2024
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