Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000528025 | SCV000622518 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-09-05 | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 453531). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (rs537377433, gnomAD 0.007%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1547 of the ATM protein (p.Ile1547Val). |
| Ambry Genetics | RCV000564870 | SCV000665513 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-13 | criteria provided, single submitter | clinical testing | The p.I1547V variant (also known as c.4639A>G), located in coding exon 30 of the ATM gene, results from an A to G substitution at nucleotide position 4639. The isoleucine at codon 1547 is replaced by valine, 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. |
| Baylor Genetics | RCV003464121 | SCV004216225 | uncertain significance | Familial cancer of breast | 2021-07-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004721408 | SCV005327798 | uncertain significance | not provided | 2024-03-20 | 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 |