Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130312 | SCV000185162 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-05 | criteria provided, single submitter | clinical testing | The p.F1491L variant (also known as c.4471T>C), located in coding exon 29 of the ATM gene, results from a T to C substitution at nucleotide position 4471. The phenylalanine at codon 1491 is replaced by leucine, an amino acid with highly similar 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. |
| Labcorp Genetics |
RCV000531385 | SCV000622504 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-01-18 | 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 1491 of the ATM protein (p.Phe1491Leu). This variant is present in population databases (rs587781944, gnomAD 0.01%). 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: 141696). 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. |
| Color Diagnostics, |
RCV000130312 | SCV000911409 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with leucine at codon 1491 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 ATM-related disorders in the literature. This variant has been identified in 1/31378 chromosomes 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. |
| Fulgent Genetics, |
RCV002492501 | SCV002776548 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2022-04-07 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003467139 | SCV004210333 | uncertain significance | Familial cancer of breast | 2023-05-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004760392 | SCV005369729 | uncertain significance | not provided | 2023-05-26 | 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 |
| Natera, |
RCV000531385 | SCV001462145 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-04-17 | no assertion criteria provided | clinical testing |