ClinVar Miner

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

dbSNP: rs2048519381
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Total submissions: 4
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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

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