Submissions for variant NM_002878.4(RAD51D):c.358A>G (p.Met120Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002301734	SCV002589901	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2022-09-12	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 120 of the RAD51D protein (p.Met120Val). This variant is not present in population databases (gnomAD no frequency). 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 RAD51D protein function. 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.
Ambry Genetics	RCV004948690	SCV005485338	likely benign	Hereditary cancer-predisposing syndrome	2024-11-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.