Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165340 | SCV000216063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | The p.N868K variant (also known as c.2604T>G), located in coding exon 16 of the RAD50 gene, results from a T to G substitution at nucleotide position 2604. The asparagine at codon 868 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in 2/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). 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. |
| Gene |
RCV000165340 | SCV000822151 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000165340 | SCV000939094 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-14 | 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 not expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 185843). This missense change has been observed in individual(s) with clinical features of RAD50-related conditions (PMID: 31159747). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 868 of the RAD50 protein (p.Asn868Lys). |