Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001210119 | SCV001381587 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2509 of the ATM protein (p.Met2509Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 940517). 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 valine 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 |
RCV002290637 | SCV002578308 | uncertain significance | not provided | 2022-04-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23532176) |
Ambry Genetics | RCV002393474 | SCV002669123 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-01 | criteria provided, single submitter | clinical testing | The p.M2509V variant (also known as c.7525A>G), located in coding exon 50 of the ATM gene, results from an A to G substitution at nucleotide position 7525. The methionine at codon 2509 is replaced by valine, an amino acid with highly similar properties. 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001210119 | SCV002080710 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-04-14 | no assertion criteria provided | clinical testing |