Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025975 | SCV001188268 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-01 | criteria provided, single submitter | clinical testing | The p.P2353T variant (also known as c.7057C>A), located in coding exon 47 of the ATM gene, results from a C to A substitution at nucleotide position 7057. The proline at codon 2353 is replaced by threonine, an amino acid with highly similar properties. 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. |
| Labcorp Genetics |
RCV001862348 | SCV002284457 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-12-25 | 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: 826801). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 2353 of the ATM protein (p.Pro2353Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. |