Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000213694 | SCV000275865 | likely benign | Hereditary cancer-predisposing syndrome | 2024-08-21 | 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. |
Color Diagnostics, |
RCV000213694 | SCV000913989 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000821518 | SCV000962277 | uncertain significance | Ataxia-telangiectasia syndrome | 2025-01-22 | 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 568 of the ATM protein (p.Arg568Gly). 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: 231883). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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. |
Prevention |
RCV004547546 | SCV004115797 | uncertain significance | ATM-related disorder | 2022-12-09 | criteria provided, single submitter | clinical testing | The ATM c.1702A>G variant is predicted to result in the amino acid substitution p.Arg568Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/231883/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV003462480 | SCV004207055 | uncertain significance | Familial cancer of breast | 2024-03-08 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000821518 | SCV002083757 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-02-25 | no assertion criteria provided | clinical testing |