Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001059108 | SCV001223717 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-03-23 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 1251 of the ATM protein (p.Cys1251Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 854135). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Ambry Genetics | RCV002348431 | SCV002622176 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-13 | criteria provided, single submitter | clinical testing | The p.C1251F variant (also known as c.3752G>T), located in coding exon 25 of the ATM gene, results from a G to T substitution at nucleotide position 3752. The cysteine at codon 1251 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998621 | SCV005622931 | uncertain significance | not provided | 2024-11-08 | criteria provided, single submitter | clinical testing | The ATM c.3752G>T (p.Cys1251Phe) variant has not been reported in individuals with ATM-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |