Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000547897 | SCV000628262 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-20 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1120 of the RAD50 protein (p.Asp1120His). This variant is present in population databases (rs764770735, gnomAD 0.002%). This missense change has been observed in individual(s) with breast cancer (PMID: 25503501). ClinVar contains an entry for this variant (Variation ID: 457447). 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. 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. |
| Ambry Genetics | RCV000547897 | SCV000663627 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-02 | criteria provided, single submitter | clinical testing | The p.D1120H variant (also known as c.3358G>C), located in coding exon 21 of the RAD50 gene, results from a G to C substitution at nucleotide position 3358. The aspartic acid at codon 1120 is replaced by histidine, an amino acid with similar properties. This alteration was previously reported in at least one individual from a cohort of 278 BRCA1/2-negative individuals with early-onset breast cancer via multiplex panel testing of 22 cancer susceptibility genes. (Maxwell KN et al. Genet. Med., 2015 Aug;17:630-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |