Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000198750 | SCV000254135 | uncertain significance | Ataxia-telangiectasia syndrome | 2016-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamine at codon 2253 of the ATM protein (p.Lys2253Gln). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ATM-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001025616 | SCV001187841 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-05 | criteria provided, single submitter | clinical testing | The p.K2253Q variant (also known as c.6757A>C), located in coding exon 45 of the ATM gene, results from an A to C substitution at nucleotide position 6757. The lysine at codon 2253 is replaced by glutamine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |