Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000212014 | SCV000209735 | uncertain significance | not provided | 2024-03-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28779002, 25186627, 28652578, 34326862, 33280026) |
| Ambry Genetics | RCV000159723 | SCV000215787 | likely benign | Hereditary cancer-predisposing syndrome | 2020-07-16 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV000197917 | SCV000254106 | uncertain significance | Ataxia-telangiectasia syndrome | 2025-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1466 of the ATM protein (p.Arg1466Gly). This variant is present in population databases (rs730881369, gnomAD 0.002%). This missense change has been observed in individual(s) with breast cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 181956). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATM protein function. 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, |
RCV000159723 | SCV000682202 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-01 | criteria provided, single submitter | clinical testing | |
| Spanish ATM Cancer Susceptibility Variant Interpretation Working Group | RCV000159723 | SCV001911461 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-17 | criteria provided, single submitter | clinical testing | The c.4396C>G (p.Arg1466Gly) variant appears only twice in the gnomAD v2.1.1 non-cancer dataset (0.0007% frequency), specifically in the European (non-Finnish) subpopulation (PM2; http://gnomad.broadinstitute.org). This missense variant is not predicted to lead to a splicing alteration as per SPiCE predictor and no splicing site is created/activated according to at least 3 splicing predictors of the set SpliceSiteFinderlike - MaxEntScan - NNSplice – GeneSplicer, but it alters the protein function / structure on the in-silico prediction reports of REVEL and VEST4 (PP3). There is no other supporting data that meet criteria for consideration. Therefore, the clinical significance of this variant is uncertain. Adapted ACMG/AMP rules applied as defined by the Spanish ATM working group: PM2 + PP3 (PMID: 33280026). |
| Baylor Genetics | RCV003467230 | SCV004209413 | uncertain significance | Familial cancer of breast | 2023-09-21 | criteria provided, single submitter | clinical testing |