Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001026345 | SCV001188708 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-13 | criteria provided, single submitter | clinical testing | The p.N246T variant (also known as c.737A>C), located in coding exon 6 of the ATM gene, results from an A to C substitution at nucleotide position 737. The asparagine at codon 246 is replaced by threonine, 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. |
Invitae | RCV001320747 | SCV001511545 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-02-03 | criteria provided, single submitter | clinical testing | 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 246 of the ATM protein (p.Asn246Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine. |