Submissions for variant NM_058216.3(RAD51C):c.727G>A (p.Gly243Ser)

dbSNP: rs2048494596

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001209524	SCV001380962	uncertain significance	Fanconi anemia complementation group O	2023-09-14	criteria provided, single submitter	clinical testing	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. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 243 of the RAD51C protein (p.Gly243Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 27616075). ClinVar contains an entry for this variant (Variation ID: 940024). 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 RAD51C protein function.
Ambry Genetics	RCV002379793	SCV002672901	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-07	criteria provided, single submitter	clinical testing	The p.G243S variant (also known as c.727G>A), located in coding exon 5 of the RAD51C gene, results from a G to A substitution at nucleotide position 727. The glycine at codon 243 is replaced by serine, an amino acid with similar properties. This alteration has been reported in an individual with a personal history of bilateral breast cancer (Kraus C et al. Int J Cancer, 2017 Jan;140:95-102). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV002379793	SCV004357124	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-31	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with serine at codon 243 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 27616075). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.