Submissions for variant NM_007294.4(BRCA1):c.2405T>G (p.Val802Gly)

dbSNP: rs1555589737

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000560561	SCV000635846	uncertain significance	Hereditary breast ovarian cancer syndrome	2020-04-10	criteria provided, single submitter	clinical testing	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: "Benign"; Align-GVGD: "Class C0". The glycine 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. 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. This sequence change replaces valine with glycine at codon 802 of the BRCA1 protein (p.Val802Gly). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glycine.
University of Washington Department of Laboratory Medicine, University of Washington	RCV003157695	SCV003847691	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).