Submissions for variant NM_058216.3(RAD51C):c.803A>G (p.Gln268Arg)

dbSNP: rs1064794654

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483316	SCV000569653	uncertain significance	not provided	2016-03-22	criteria provided, single submitter	clinical testing	This variant is denoted RAD51C c.803A>G at the cDNA level, p.Gln268Arg (Q268R) at the protein level, and results in the change of a Glutamine to an Arginine (CAA>CGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Gln268Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. RAD51C Gln268Arg occurs at a position that is conserved across species and is located within the ATPase domain (Kim 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether RAD51C Gln268Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae	RCV001050418	SCV001214525	uncertain significance	Fanconi anemia complementation group O	2023-04-30	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. 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. ClinVar contains an entry for this variant (Variation ID: 420709). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 268 of the RAD51C protein (p.Gln268Arg).
Ambry Genetics	RCV002413326	SCV002675548	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-21	criteria provided, single submitter	clinical testing	The p.Q268R variant (also known as c.803A>G), located in coding exon 5 of the RAD51C gene, results from an A to G substitution at nucleotide position 803. The glutamine at codon 268 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.