ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.10682G>A (p.Arg3561His)

gnomAD frequency: 0.00001  dbSNP: rs1064796932
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485981 SCV000574162 uncertain significance not provided 2017-03-23 criteria provided, single submitter clinical testing The R3561H variant in the DYNC1H1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R3561H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R3561H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. While this substitution occurs at a position that is conserved across species, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R3561H as a variant of uncertain significance.
Invitae RCV000698259 SCV000826914 uncertain significance Charcot-Marie-Tooth disease axonal type 2O 2022-05-28 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3561 of the DYNC1H1 protein (p.Arg3561His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYNC1H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 424360). 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 not expected to disrupt DYNC1H1 protein function.

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