Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001999121 | SCV002286508 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-12-19 | 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 been observed in individual(s) affected with ataxia telangiectasia (PMID: 12815592). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with threonine at codon 2717 of the ATM protein (p.Lys2717Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. |
Ambry Genetics | RCV002423213 | SCV002680341 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-09 | criteria provided, single submitter | clinical testing | The p.K2717T variant (also known as c.8150A>C), located in coding exon 54 of the ATM gene, results from an A to C substitution at nucleotide position 8150. The lysine at codon 2717 is replaced by threonine, an amino acid with similar properties. This variant has been reported in a compound heterozygous state with an additional ATM mutation in an individual diagnosed with ataxia-telangiectasia (Mitui M et al. Hum Mutat, 2003 Jul;22:43-50). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |