Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000525635 | SCV000622268 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-06-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 513 of the ATM protein (p.Gln513Arg). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with a personal and/or family history of hereditary breast and/or ovarian cancer (PMID: 27067391). ClinVar contains an entry for this variant (Variation ID: 453375). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Gene |
RCV001797094 | SCV002038802 | uncertain significance | not provided | 2021-12-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in patients with suspected hereditary breast and ovarian cancer (Mucaki 2016); This variant is associated with the following publications: (PMID: 27067391) |
| Ambry Genetics | RCV002404355 | SCV002705850 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-23 | criteria provided, single submitter | clinical testing | The p.Q513R variant (also known as c.1538A>G), located in coding exon 9 of the ATM gene, results from an A to G substitution at nucleotide position 1538. The glutamine at codon 513 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in patients referred for hereditary breast and ovarian cancer testing (Mucaki EJ et al. BMC Med Genomics, 2016 Apr;9:19; Matis TS et al. NPJ Breast Cancer, 2021 Aug;7:109). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |