Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000811461 | SCV000951728 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-09-15 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 655318). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 2348 of the ATM protein (p.Thr2348Met). |
Ambry Genetics | RCV002363099 | SCV002662090 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-11 | criteria provided, single submitter | clinical testing | The p.T2348M variant (also known as c.7043C>T), located in coding exon 47 of the ATM gene, results from a C to T substitution at nucleotide position 7043. The threonine at codon 2348 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Color Diagnostics, |
RCV002363099 | SCV004361827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with methionine at codon 2348 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Natera, |
RCV000811461 | SCV002080097 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-25 | no assertion criteria provided | clinical testing |