Submissions for variant NM_058216.3(RAD51C):c.284A>G (p.His95Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003617656	SCV004474394	uncertain significance	Fanconi anemia complementation group O	2023-06-09	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 variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 95 of the RAD51C protein (p.His95Arg). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. 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	RCV004950589	SCV005490135	uncertain significance	Hereditary cancer-predisposing syndrome	2024-09-08	criteria provided, single submitter	clinical testing	The p.H95R variant (also known as c.284A>G), located in coding exon 2 of the RAD51C gene, results from an A to G substitution at nucleotide position 284. The histidine at codon 95 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.