Submissions for variant NM_058216.3(RAD51C):c.293G>T (p.Gly98Val)

dbSNP: rs1060502586

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000648225	SCV000770039	uncertain significance	Fanconi anemia complementation group O	2022-03-14	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 538765). 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 glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 98 of the RAD51C protein (p.Gly98Val).
Color Diagnostics, LLC DBA Color Health	RCV001191944	SCV001359885	uncertain significance	Hereditary cancer-predisposing syndrome	2019-09-27	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 98 of the RAD51C protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Ambry Genetics	RCV001191944	SCV002750227	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-20	criteria provided, single submitter	clinical testing	The p.G98V variant (also known as c.293G>T), located in coding exon 2 of the RAD51C gene, results from a G to T substitution at nucleotide position 293. The glycine at codon 98 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not 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.
Baylor Genetics	RCV003459546	SCV004207996	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2023-06-05	criteria provided, single submitter	clinical testing