Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001020976 | SCV001182530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-02 | criteria provided, single submitter | clinical testing | The p.T1242A variant (also known as c.3724A>G), located in coding exon 24 of the ATM gene, results from an A to G substitution at nucleotide position 3724. The threonine at codon 1242 is replaced by alanine, an amino acid with 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. |
Invitae | RCV001342635 | SCV001536579 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1242 of the ATM protein (p.Thr1242Ala). 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: 824127). 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 ATM 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 |
RCV001570783 | SCV001795133 | uncertain significance | not provided | 2019-08-07 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |