Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002028572 | SCV002283736 | uncertain significance | not provided | 2023-08-04 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 397 of the TWNK protein (p.Asp397Gly). This variant is present in population databases (rs751144474, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of TWNK-related conditions (PMID: 28776642). ClinVar contains an entry for this variant (Variation ID: 1496673). 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 TWNK 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. |
Fulgent Genetics, |
RCV002479711 | SCV002778590 | uncertain significance | Infantile onset spinocerebellar ataxia; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Perrault syndrome 5 | 2022-01-20 | criteria provided, single submitter | clinical testing |