Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genetics and Genomics, |
RCV001269843 | SCV001450144 | pathogenic | not provided | 2015-10-21 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003586144 | SCV004271058 | likely pathogenic | Dystonic disorder | 2023-05-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 288 of the TOR1A protein (p.Arg288Gln). This variant is present in population databases (rs727502811, gnomAD 0.03%). This missense change has been observed in individuals with autosomal dominant dystonia (PMID: 18477710, 31321303). ClinVar contains an entry for this variant (Variation ID: 162491). 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 TOR1A protein function. Experimental studies have shown that this missense change affects TOR1A function (PMID: 18477710, 24930953, 32243914). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV000149874 | SCV000196728 | pathogenic | Early-onset generalized limb-onset dystonia | 2014-09-01 | no assertion criteria provided | literature only | |
Gene |
RCV000149874 | SCV000328701 | not provided | Early-onset generalized limb-onset dystonia | no assertion provided | literature only |