Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003586123 | SCV004296127 | pathogenic | Jeune thoracic dystrophy | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1240 of the DYNC2H1 protein (p.Ile1240Thr). This variant is present in population databases (rs137853028, gnomAD 0.007%). This missense change has been observed in individual(s) with asphyxiating thoracic dystrophy (PMID: 19442771, 23339108, 23456818). 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: 6504). 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%. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000006877 | SCV000027073 | pathogenic | Asphyxiating thoracic dystrophy 3 | 2009-05-01 | no assertion criteria provided | literature only |