ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1243G>T (p.Val415Phe)

dbSNP: rs587782770
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533425 SCV000635786 uncertain significance Hereditary breast ovarian cancer syndrome 2017-04-11 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 415 of the BRCA1 protein (p.Val415Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The phenylalanine 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157685 SCV003846079 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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