Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580979 | SCV000682387 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001308636 | SCV001498098 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-06-03 | 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 (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. ClinVar contains an entry for this variant (Variation ID: 489585). This variant is present in population databases (rs757293178, ExAC 0.003%). This sequence change replaces lysine with methionine at codon 2363 of the ATM protein (p.Lys2363Met). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and methionine. |
Ambry Genetics | RCV000580979 | SCV002662559 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-13 | criteria provided, single submitter | clinical testing | The p.K2363M variant (also known as c.7088A>T), located in coding exon 47 of the ATM gene, results from an A to T substitution at nucleotide position 7088. The lysine at codon 2363 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |