Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000516108 | SCV000951059 | pathogenic | Jeune thoracic dystrophy | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 384 of the DYNC2H1 protein (p.Ala384Val). This variant is present in population databases (rs369614706, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of short rib polydactyly syndrome (PMID: 25982780, 29620724; 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: 446677). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DYNC2H1 protein function. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001577701 | SCV001805125 | likely pathogenic | not provided | 2019-10-01 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32333414, 31589614, 29359448, 29620724, 29068549, 29458881, 25982780, 27323140) |
Dan Cohn Lab, |
RCV000516108 | SCV000612105 | pathogenic | Jeune thoracic dystrophy | 2017-06-01 | no assertion criteria provided | research | |
University of Washington Center for Mendelian Genomics, |
RCV000516108 | SCV001479534 | likely pathogenic | Jeune thoracic dystrophy | no assertion criteria provided | research |