Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000803383 | SCV000943252 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 130 of the ATM protein (p.Asp130Glu). 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: 648619). 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. |
| Gene |
RCV001766667 | SCV002000268 | uncertain significance | not provided | 2020-01-16 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 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 |
| Ambry Genetics | RCV002370131 | SCV002624061 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-17 | criteria provided, single submitter | clinical testing | The p.D130E variant (also known as c.390T>G), located in coding exon 4 of the ATM gene, results from a T to G substitution at nucleotide position 390. The aspartic acid at codon 130 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration was identified in a cohort of 1040 patients with advanced cancer; however, specific clinical information on this individual was not provided (Mandelker D et al. JAMA, 2017 09;318:825-835). 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. |
| Baylor Genetics | RCV004569600 | SCV005057017 | uncertain significance | Familial cancer of breast | 2024-02-06 | criteria provided, single submitter | clinical testing |