Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001014548 | SCV001175267 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-16 | criteria provided, single submitter | clinical testing | The p.T710A variant (also known as c.2128A>G), located in coding exon 13 of the ATM gene, results from an A to G substitution at nucleotide position 2128. The threonine at codon 710 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly 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 | RCV001203652 | SCV001374826 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 710 of the ATM protein (p.Thr710Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs750506930, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine 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. |