Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567342 | SCV000665608 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-20 | criteria provided, single submitter | clinical testing | The p.L1449F variant (also known as c.4347A>C), located in coding exon 28 of the ATM gene, results from an A to C substitution at nucleotide position 4347. The leucine at codon 1449 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001235108 | SCV001407777 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1449 of the ATM protein (p.Leu1449Phe). This variant is present in population databases (rs764787081, gnomAD 0.003%). 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: 481300). 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: "Benign"; Align-GVGD: "Class C15"). 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. |