Submissions for variant NM_007294.4(BRCA1):c.1929T>G (p.Ser643Arg)

dbSNP: rs1060502361

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000459628	SCV000549406	uncertain significance	Hereditary breast ovarian cancer syndrome	2016-05-07	criteria provided, single submitter	clinical testing	In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 serine with arginine at codon 643 of the BRCA1 protein (p.Ser643Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine.
University of Washington Department of Laboratory Medicine, University of Washington	RCV003157521	SCV003849628	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).