Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000204669 | SCV000259682 | uncertain significance | Ataxia-telangiectasia syndrome | 2025-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1334 of the ATM protein (p.His1334Arg). This variant is present in population databases (rs780865776, gnomAD 0.003%). 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: 219675). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. 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 | RCV000569521 | SCV000660682 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-30 | criteria provided, single submitter | clinical testing | The p.H1334R variant (also known as c.4001A>G), located in coding exon 26 of the ATM gene, results from an A to G substitution at nucleotide position 4001. The histidine at codon 1334 is replaced by arginine, 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. |
| Color Diagnostics, |
RCV000569521 | SCV001340517 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-02 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with arginine at codon 1334 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 been identified in 2/248350 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. |
| Sema4, |
RCV000569521 | SCV002528917 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-15 | criteria provided, single submitter | curation | |
| Gene |
RCV004725060 | SCV005332929 | 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 |