Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000700122 | SCV000828864 | uncertain significance | Fanconi anemia complementation group O | 2018-05-02 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 284 of the RAD51C protein (p.Asn284Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51C-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
Ambry Genetics | RCV002442493 | SCV002681554 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-03 | criteria provided, single submitter | clinical testing | The p.N284S variant (also known as c.851A>G), located in coding exon 6 of the RAD51C gene, results from an A to G substitution at nucleotide position 851. The asparagine at codon 284 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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. |