Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000697868 | SCV000826501 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 55 of the ATM protein (p.Leu55Trp). 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: 575605). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. 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 | RCV002397431 | SCV002705543 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-24 | criteria provided, single submitter | clinical testing | The p.L55W variant (also known as c.164T>G), located in coding exon 2 of the ATM gene, results from a T to G substitution at nucleotide position 164. The leucine at codon 55 is replaced by tryptophan, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Baylor Genetics | RCV004569345 | SCV005056914 | uncertain significance | Familial cancer of breast | 2024-03-05 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004723098 | SCV005337345 | uncertain significance | ATM-related disorder | 2024-08-27 | no assertion criteria provided | clinical testing | The ATM c.164T>G variant is predicted to result in the amino acid substitution p.Leu55Trp. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/575605/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |