Submissions for variant NM_007294.4(BRCA1):c.3419G>A (p.Ser1140Asn)

dbSNP: rs2053590016

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001057074	SCV001221550	uncertain significance	Hereditary breast ovarian cancer syndrome	2019-12-13	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with BRCA1-related conditions. 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. 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 asparagine 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 1140 of the BRCA1 protein (p.Ser1140Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine.
University of Washington Department of Laboratory Medicine, University of Washington	RCV003158376	SCV003848756	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).