Submissions for variant NM_058216.3(RAD51C):c.53C>T (p.Pro18Leu)

gnomAD frequency: 0.00001  dbSNP: rs754498936

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000566801	SCV000663756	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-13	criteria provided, single submitter	clinical testing	The p.P18L variant (also known as c.53C>T), located in coding exon 1 of the RAD51C gene, results from a C to T substitution at nucleotide position 53. The proline at codon 18 is replaced by leucine, an amino acid with 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.
Color Diagnostics, LLC DBA Color Health	RCV000566801	SCV000691245	uncertain significance	Hereditary cancer-predisposing syndrome	2022-04-27	criteria provided, single submitter	clinical testing	This missense variant replaces proline with leucine at codon 18 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 ovarian cancer in the literature. This variant has been identified in 3/251452 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	RCV000648267	SCV000770081	uncertain significance	Fanconi anemia complementation group O	2023-03-22	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 not expected to disrupt RAD51C protein function. ClinVar contains an entry for this variant (Variation ID: 480491). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is present in population databases (rs754498936, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 18 of the RAD51C protein (p.Pro18Leu).