Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV001530866 | SCV000272468 | uncertain significance | not provided | 2019-06-05 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
Gene |
RCV001530866 | SCV001745771 | likely benign | not provided | 2021-02-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001530866 | SCV002151697 | uncertain significance | not provided | 2022-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 106 of the SYNE4 protein (p.Gln106Pro). This variant is present in population databases (rs200994810, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SYNE4-related conditions. ClinVar contains an entry for this variant (Variation ID: 229283). 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 expected to disrupt SYNE4 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. |