Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001219390 | SCV001391326 | uncertain significance | Ataxia-telangiectasia syndrome | 2019-04-26 | 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. This sequence change replaces methionine with isoleucine at codon 2734 of the ATM protein (p.Met2734Ile). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with 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 and their clinical significance is uncertain. |
| Ambry Genetics | RCV004671268 | SCV005173022 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-19 | criteria provided, single submitter | clinical testing | The p.M2734I variant (also known as c.8202G>A), located in coding exon 55 of the ATM gene, results from a G to A substitution at nucleotide position 8202. The methionine at codon 2734 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |