Submissions for variant NM_001377.3(DYNC2H1):c.4553G>A (p.Cys1518Tyr)

dbSNP: rs1555053115

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000516112	SCV004538837	likely pathogenic	Jeune thoracic dystrophy	2022-11-28	criteria provided, single submitter	clinical testing	This missense change has been observed in individual(s) with DYNC2H1-related conditions (PMID: 29068549). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1518 of the DYNC2H1 protein (p.Cys1518Tyr). ClinVar contains an entry for this variant (Variation ID: 446596). 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. 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.
Dan Cohn Lab, University Of California Los Angeles	RCV000516112	SCV000611996	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000516112	SCV001479730	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research