Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000774982 | SCV000909075 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-08-27 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with leucine at codon 1336 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer 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. |
| Labcorp Genetics |
RCV000793212 | SCV000932553 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-04-08 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1336 of the ATM protein (p.Phe1336Leu). 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: 630066). 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. 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 | RCV000774982 | SCV002624530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-31 | criteria provided, single submitter | clinical testing | The p.F1336L variant (also known as c.4006T>C), located in coding exon 26 of the ATM gene, results from a T to C substitution at nucleotide position 4006. The phenylalanine at codon 1336 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not 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. |
| Gene |
RCV003322820 | SCV004028416 | uncertain significance | not provided | 2023-08-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003465697 | SCV004209409 | uncertain significance | Familial cancer of breast | 2023-09-21 | criteria provided, single submitter | clinical testing |