Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000218006 | SCV000278325 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-26 | criteria provided, single submitter | clinical testing | The p.H993D variant (also known as c.2977C>G), located in coding exon 19 of the RAD50 gene, results from a C to G substitution at nucleotide position 2977. The histidine at codon 993 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is poorly 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 | RCV000218006 | SCV002275234 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 233864). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 993 of the RAD50 protein (p.His993Asp). |