Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001225367 | SCV001397647 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-05-12 | criteria provided, single submitter | clinical testing | 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 953121). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1028 of the ATM protein (p.Leu1028Pro). |
Gene |
RCV001760219 | SCV002000187 | uncertain significance | not provided | 2020-10-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002319679 | SCV002608784 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.L1028P variant (also known as c.3083T>C), located in coding exon 20 of the ATM gene, results from a T to C substitution at nucleotide position 3083. The leucine at codon 1028 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV002319679 | SCV004361708 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-25 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 1028 of the ATM protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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. |
Baylor Genetics | RCV004570554 | SCV005053020 | uncertain significance | Familial cancer of breast | 2023-11-19 | criteria provided, single submitter | clinical testing |