Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000623202 | SCV000742000 | uncertain significance | Inborn genetic diseases | 2016-11-25 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003748268 | SCV004551672 | likely pathogenic | Jeune thoracic dystrophy | 2024-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 535 of the DYNC2H1 protein (p.Phe535Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of DYNC2H1-related conditions (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: 521417). 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 DYNC2H1 protein function with a positive predictive value of 95%. 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. |