Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485506 | SCV000566173 | uncertain significance | not provided | 2020-07-27 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); 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 |
| Labcorp Genetics |
RCV001061923 | SCV001226687 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 1727 of the ATM protein (p.Val1727Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC 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: 418824). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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, |
RCV001525070 | SCV001735078 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 1727 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). 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. |
| Sema4, |
RCV001525070 | SCV002536105 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-11 | criteria provided, single submitter | curation | |
| Ambry Genetics | RCV001525070 | SCV003868814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-06 | criteria provided, single submitter | clinical testing | The p.V1727I variant (also known as c.5179G>A), located in coding exon 34 of the ATM gene, results from a G to A substitution at nucleotide position 5179. The valine at codon 1727 is replaced by isoleucine, 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. |
| Baylor Genetics | RCV003470535 | SCV004210270 | uncertain significance | Familial cancer of breast | 2023-06-16 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001061923 | SCV001452310 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |