Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000815837 | SCV000956310 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 656 of the ATM protein (p.Thr656Ile). This variant is present in population databases (rs754800755, gnomAD 0.006%). 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: 658920). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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 | RCV002422826 | SCV002720172 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-18 | criteria provided, single submitter | clinical testing | The p.T656I variant (also known as c.1967C>T), located in coding exon 12 of the ATM gene, results from a C to T substitution at nucleotide position 1967. The threonine at codon 656 is replaced by isoleucine, an amino acid with similar properties. 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. |