ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.751C>T (p.Arg251Cys) (rs879253979)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414974 SCV000492853 likely pathogenic Myopathy; Pes cavus; Hammertoe; Distal lower limb amyotrophy 2015-05-11 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512659 SCV000608712 uncertain significance not provided 2016-05-01 criteria provided, single submitter clinical testing
Invitae RCV000649558 SCV000771387 pathogenic Charcot-Marie-Tooth disease, axonal, type 2O 2019-09-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 251 of the DYNC1H1 protein (p.Arg251Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in several individuals affected with spinal muscular atrophy with lower extremity predominant (SMALED) (PMID: 30122514). This variant has also been reported in an individual affected with an abnormality of the nervous system (PMID: 26633542). ClinVar contains an entry for this variant (Variation ID: 374099). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg251His) has been determined to be likely pathogenic (PMID: 26392352, Invitae). This suggests that the arginine residue is critical for DYNC1H1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266345 SCV001444519 likely pathogenic Inborn genetic diseases 2019-12-19 criteria provided, single submitter clinical testing

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.