Submissions for variant NM_058216.3(RAD51C):c.335G>T (p.Gly112Val)

dbSNP: rs370212314

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589409	SCV000699804	uncertain significance	not specified	2021-02-15	criteria provided, single submitter	clinical testing	Variant summary: RAD51C c.335G>T (p.Gly112Val) results in a non-conservative amino acid change located in the DNA recombination and repair protein Rad51-like, C-terminal domain (IPR013632) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 256840 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.335G>T has been reported in the literature in at least one individual affected with ovarian cancer (e.g. Song_2015). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001223386	SCV001395533	uncertain significance	Fanconi anemia complementation group O	2023-04-12	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 expected to disrupt RAD51C protein function. ClinVar contains an entry for this variant (Variation ID: 496502). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26261251). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 112 of the RAD51C protein (p.Gly112Val).