Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478770 | SCV000572620 | uncertain significance | not provided | 2020-06-03 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV000553522 | SCV000622496 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1460 of the ATM protein (p.Ala1460Val). 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: 423001). 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, |
RCV000777910 | SCV000913942 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000777910 | SCV002629053 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-12 | criteria provided, single submitter | clinical testing | The p.A1460V variant (also known as c.4379C>T), located in coding exon 28 of the ATM gene, results from a C to T substitution at nucleotide position 4379. The alanine at codon 1460 is replaced by valine, an amino acid with similar properties. In one study of germline alterations in patients with chronic lymphocytic leukemia (CLL), this alteration was not detected in 516 patients with CLL but was identified in 1/8,920 matched healthy control patients (Tiao G et al. Leukemia, 2017 10;31:2244-2247). 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. |
| Baylor Genetics | RCV004568207 | SCV005057134 | uncertain significance | Familial cancer of breast | 2023-12-20 | criteria provided, single submitter | clinical testing |