Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001758648 | SCV001995639 | uncertain significance | not provided | 2024-05-13 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this missense variant does not alter protein structure/function |
Labcorp Genetics |
RCV001868504 | SCV002302545 | uncertain significance | Loeys-Dietz syndrome 2 | 2022-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 588 of the TMPO protein (p.Phe588Ser). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TMPO protein function. ClinVar contains an entry for this variant (Variation ID: 1311139). This variant has not been reported in the literature in individuals affected with TMPO-related conditions. This variant is present in population databases (rs571417296, gnomAD 0.04%). |
Ambry Genetics | RCV004040224 | SCV002713334 | likely benign | not specified | 2022-03-03 | 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. |