Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000231434 | SCV000289050 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-21 | 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 expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 240232). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs781678144, gnomAD 0.02%). This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1045 of the RAD50 protein (p.Met1045Arg). |
Ambry Genetics | RCV000231434 | SCV000663635 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-09 | criteria provided, single submitter | clinical testing | The p.M1045R variant (also known as c.3134T>G), located in coding exon 20 of the RAD50 gene, results from a T to G substitution at nucleotide position 3134. The methionine at codon 1045 is replaced by arginine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |