ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1441C>G (p.Leu481Val) (rs1397842308)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501590 SCV000591332 likely benign not specified 2013-08-06 criteria provided, single submitter clinical testing
Invitae RCV000555910 SCV000635797 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-04-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 481 of the BRCA1 protein (p.Leu481Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in a single family affected with hereditary breast/ovarian cancer (PMID: 24916970). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000575549 SCV000665910 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-26 criteria provided, single submitter clinical testing Insufficient evidence
Mendelics RCV000989903 SCV001140604 uncertain significance Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735490 SCV000863628 likely benign Breast and/or ovarian cancer 2013-06-03 no assertion criteria provided clinical testing

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