Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022833 | SCV001184614 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-22 | criteria provided, single submitter | clinical testing | The p.N1549K variant (also known as c.4647C>G), located in coding exon 30 of the ATM gene, results from a C to G substitution at nucleotide position 4647. The asparagine at codon 1549 is replaced by lysine, 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. |
| Labcorp Genetics |
RCV001228771 | SCV001401188 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-09-27 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 lysine at codon 1549 of the ATM protein (p.Asn1549Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. |