Submissions for variant NM_007294.4(BRCA1):c.3542T>G (p.Val1181Gly)

dbSNP: rs80357032

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001050873	SCV001215002	uncertain significance	Hereditary breast ovarian cancer syndrome	2020-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces valine with glycine at codon 1181 of the BRCA1 protein (p.Val1181Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 847346).
University of Washington Department of Laboratory Medicine, University of Washington	RCV003158360	SCV003850304	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).