Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000222585 | SCV000275398 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing | The p.I819M variant (also known as c.2457A>G), located in coding exon 15 of the RAD50 gene, results from an A to G substitution at nucleotide position 2457. The isoleucine at codon 819 is replaced by methionine, an amino acid with highly 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 | RCV000222585 | SCV000828513 | 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 not expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 231522). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs143554330, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 819 of the RAD50 protein (p.Ile819Met). |
Baylor Genetics | RCV003469034 | SCV004207363 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-07-25 | criteria provided, single submitter | clinical testing |