ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4903G>A (p.Glu1635Lys) (rs200432771)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410023 SCV000489521 uncertain significance Breast-ovarian cancer, familial 1 2016-10-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509803 SCV000608213 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-16 criteria provided, single submitter clinical testing The p.E1635K variant (also known as c.4903G>A), located in coding exon 14 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4903. The glutamic acid at codon 1635 is replaced by lysine, an amino acid with similar properties. This alteration has been reported as a secondary finding in 1 of 572 individuals undergoing exome sequencing in subjects ascertained for atherosclerosis phenotypes (Johnston JJ et al. Am. J. Hum. Genet. 2012 Jul;91:97-108). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769712 SCV000901132 uncertain significance Breast and/or ovarian cancer 2016-12-28 criteria provided, single submitter clinical testing
Invitae RCV001071216 SCV001236507 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1635 of the BRCA1 protein (p.Glu1635Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ovarian cancer (PMID: 21218378). ClinVar contains an entry for this variant (Variation ID: 41829). This variant has been reported not to substantially affect BRCA1 protein function (PMID: 30209399). 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.
Research and Development, ARUP Laboratories RCV001659949 SCV001878396 uncertain significance Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034755 SCV000043154 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Brotman Baty Institute,University of Washington RCV000410023 SCV001243813 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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