Submissions for variant NM_058216.3(RAD51C):c.86C>T (p.Ser29Phe)

dbSNP: rs876659683

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000223596	SCV000276397	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-23	criteria provided, single submitter	clinical testing	The p.S29F variant (also known as c.86C>T), located in coding exon 1 of the RAD51C gene, results from a C to T substitution at nucleotide position 86. The serine at codon 29 is replaced by phenylalanine, an amino acid with highly 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586089	SCV000699828	uncertain significance	not provided	2016-09-06	criteria provided, single submitter	clinical testing	Variant summary: The RAD51C c.86C>T (p.Ser29Phe) variant involves the alteration of a non-conserved nucleotide. Ser29 is not conserved across species and is not located in a known functional domain; additionally, 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). However, the variant has not been evaluated for functional impact by in vivo/vitro studies. This variant was absent in 121294 control chromosomes and has not, to our knowledge, been reported in affected individuals via publications. One clinical diagnostic laboratory classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae	RCV000648262	SCV000770076	uncertain significance	Fanconi anemia complementation group O	2023-12-16	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 29 of the RAD51C protein (p.Ser29Phe). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 232301). 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.
Mendelics	RCV002247658	SCV002519244	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000586089	SCV003931126	uncertain significance	not provided	2022-12-09	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics	RCV003469054	SCV004207978	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2023-07-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000223596	SCV004357090	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-29	criteria provided, single submitter	clinical testing	This missense variant replaces serine with phenylalanine at codon 29 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251474 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.