ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.2357G>A (p.Arg786His)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002292161 SCV002584445 uncertain significance not provided 2022-04-11 criteria provided, single submitter clinical testing Previously reported as a variant of uncertain significance in an individual with demyelinating polyneuropathy (Vaeth et al., 2019); 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: 29653220, 25609763, 25512093, 26100331)
Ambry Genetics RCV003289501 SCV003960639 uncertain significance Inborn genetic diseases 2023-05-08 criteria provided, single submitter clinical testing The c.2357G>A (p.R786H) alteration is located in exon 8 (coding exon 8) of the DYNC1H1 gene. This alteration results from a G to A substitution at nucleotide position 2357, causing the arginine (R) at amino acid position 786 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003642989 SCV004551715 likely pathogenic Charcot-Marie-Tooth disease axonal type 2O 2023-03-22 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.01%). 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. 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: 1710874). This missense change has been observed in individuals with clinical features of DYNC1H1-related conditions (PMID: 29653220; Invitae). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 786 of the DYNC1H1 protein (p.Arg786His).

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