Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003556197 | SCV004295691 | pathogenic | not provided | 2023-07-10 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 441 of the TWNK protein (p.Trp441Gly). This variant is present in population databases (rs672601361, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive Perrault syndrome (PMID: 25355836). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162050). 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 TWNK protein function. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000149472 | SCV000196116 | pathogenic | Perrault syndrome 5 | 2014-11-25 | no assertion criteria provided | literature only | |
Gene |
RCV002516007 | SCV003525962 | not provided | Perrault syndrome | no assertion provided | literature only |