Submissions for variant NM_001376.5(DYNC1H1):c.10030C>T (p.Arg3344Trp)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 4

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001664806	SCV001875130	pathogenic	not provided	2023-05-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29671837, 26100331, 25512093, 25609763)
Invitae	RCV003642958	SCV004551716	likely pathogenic	Charcot-Marie-Tooth disease axonal type 2O	2022-12-18	criteria provided, single submitter	clinical testing	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. This variant disrupts the p.Arg3344 amino acid residue in DYNC1H1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23603762, 28196890). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 DYNC1H1 protein function. ClinVar contains an entry for this variant (Variation ID: 996573). This missense change has been observed in individual(s) with lissencephaly (PMID: 29671837). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3344 of the DYNC1H1 protein (p.Arg3344Trp).
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291069	SCV001479432	likely pathogenic	Lissencephaly		no assertion criteria provided	research
Yale Center for Mendelian Genomics, Yale University	RCV001849500	SCV002106986	likely pathogenic	Seizure	2021-04-05	no assertion criteria provided	literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.