Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001316218 | SCV001506825 | pathogenic | Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 | 2024-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 495 of the WDR19 protein (p.Gly495Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with WDR19-related conditions (PMID: 24504730, 29068549; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 446641). 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 WDR19 protein function with a positive predictive value of 80%. This variant disrupts the p.Gly495 amino acid residue in WDR19. Other variant(s) that disrupt this residue have been observed in individuals with WDR19-related conditions (PMID: 25726036), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Dan Cohn Lab, |
RCV000516069 | SCV000612053 | pathogenic | Jeune thoracic dystrophy | 2017-06-01 | no assertion criteria provided | research | |
University of Washington Center for Mendelian Genomics, |
RCV000516069 | SCV001479440 | likely pathogenic | Jeune thoracic dystrophy | no assertion criteria provided | research |