Submissions for variant NM_007294.4(BRCA1):c.1967A>G (p.Asn656Ser)

dbSNP: rs397508925

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000584436	SCV000688357	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000584436	SCV001174501	uncertain significance	Hereditary cancer-predisposing syndrome	2018-12-07	criteria provided, single submitter	clinical testing	The c.1967A>G (p.N656S) alteration is located in exon 10 (coding exon 9) of the BRCA1 gene. This alteration results from a A to G substitution at nucleotide position 1967, causing the asparagine (N) at amino acid position 656 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001306991	SCV001496384	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 656 of the BRCA1 protein (p.Asn656Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 12872263). This variant is also known as 2086A>G. ClinVar contains an entry for this variant (Variation ID: 54422). 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 with a negative predictive value of 95%. 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.
University of Washington Department of Laboratory Medicine, University of Washington	RCV000584436	SCV003849597	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).
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000576937	SCV000679580	not provided	Familial cancer of breast		no assertion provided	literature only