Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573480 | SCV000671832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | The p.N340Y variant (also known as c.1018A>T), located in coding exon 7 of the RAD50 gene, results from an A to T substitution at nucleotide position 1018. The asparagine at codon 340 is replaced by tyrosine, an amino acid with dissimilar 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 | RCV000573480 | SCV003278508 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RAD50-related conditions. 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: 484691). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 340 of the RAD50 protein (p.Asn340Tyr). |