Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013931 | SCV001174575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-30 | criteria provided, single submitter | clinical testing | The p.K66N variant (also known as c.198A>T), located in coding exon 3 of the ATM gene, results from an A to T substitution at nucleotide position 198. The lysine at codon 66 is replaced by asparagine, an amino acid with similar properties. This amino acid position is 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 | RCV001342603 | SCV001536547 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 66 of the ATM protein (p.Lys66Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC 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: 820455). 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 asparagine 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. |