Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001021208 | SCV001182790 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-11 | criteria provided, single submitter | clinical testing | The p.V127A variant (also known as c.380T>C), located in coding exon 4 of the RAD50 gene, results from a T to C substitution at nucleotide position 380. The valine at codon 127 is replaced by alanine, 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. |
Invitae | RCV001021208 | SCV001223460 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-06 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 127 of the RAD50 protein (p.Val127Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. |