Submissions for variant NM_058216.3(RAD51C):c.868A>T (p.Ile290Phe)

dbSNP: rs2048891385

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001186423	SCV001352825	uncertain significance	Hereditary cancer-predisposing syndrome	2022-07-25	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with phenylalanine at codon 290 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001876185	SCV002133992	uncertain significance	Fanconi anemia complementation group O	2021-03-17	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 missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 924832). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with phenylalanine at codon 290 of the RAD51C protein (p.Ile290Phe). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and phenylalanine.