Submissions for variant NM_058216.3(RAD51C):c.440G>A (p.Cys147Tyr)

dbSNP: rs764177838

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000570438	SCV000671920	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-06	criteria provided, single submitter	clinical testing	The p.C147Y variant (also known as c.440G>A), located in coding exon 3 of the RAD51C gene, results from a G to A substitution at nucleotide position 440. The cysteine at codon 147 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.analyses, respectively.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000986009	SCV001134786	uncertain significance	not provided	2019-03-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000570438	SCV002051966	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-04	criteria provided, single submitter	clinical testing	This missense variant replaces cysteine with tyrosine at codon 147 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). A functional study has reported that this variant does not affect RAD51C in a homology-directed DNA repair assay and in a RAD51 foci formation assay (PMID: 37253112). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251488 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858344	SCV002156132	uncertain significance	Fanconi anemia complementation group O	2023-10-27	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 147 of the RAD51C protein (p.Cys147Tyr). This variant is present in population databases (rs764177838, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 484757). 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 with a negative predictive value of 80%. 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.
Baylor Genetics	RCV004569244	SCV005052684	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2024-03-19	criteria provided, single submitter	clinical testing