Submissions for variant NM_058216.3(RAD51C):c.451G>A (p.Val151Met)

gnomAD frequency: 0.00002  dbSNP: rs753912045

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000218803	SCV000278520	uncertain significance	Hereditary cancer-predisposing syndrome	2024-05-02	criteria provided, single submitter	clinical testing	The p.V151M variant (also known as c.451G>A), located in coding exon 3 of the RAD51C gene, results from a G to A substitution at nucleotide position 451. The valine at codon 151 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is 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.
GeneDx	RCV000657007	SCV000566222	uncertain significance	not provided	2021-01-26	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago	RCV000486372	SCV000596688	uncertain significance	not specified	2015-11-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576264	SCV000676960	uncertain significance	Fanconi anemia complementation group O	2023-12-24	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 151 of the RAD51C protein (p.Val151Met). This variant is present in population databases (rs753912045, gnomAD 0.02%). 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: 234035). 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.
Color Diagnostics, LLC DBA Color Health	RCV000218803	SCV000686353	uncertain significance	Hereditary cancer-predisposing syndrome	2019-11-19	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 151 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). 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 been identified in 5/251484 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.
Fulgent Genetics, Fulgent Genetics	RCV002478818	SCV002784325	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2022-04-26	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV003338470	SCV004047786	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3		criteria provided, single submitter	clinical testing	The missense c.451G>A (p.Val151Met) variant in RAD51C gene has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Val151Met variant is observed in 0.001% alleles in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Val at position 151 is changed to a Met changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain significance.
Baylor Genetics	RCV003338470	SCV004208009	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2024-02-01	criteria provided, single submitter	clinical testing