ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.752G>A (p.Arg251His) (rs794727634)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000178163 SCV000230170 uncertain significance not provided 2014-11-23 criteria provided, single submitter clinical testing
Invitae RCV000548783 SCV000651666 pathogenic Charcot-Marie-Tooth disease, axonal, type 2O 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 251 of the DYNC1H1 protein (p.Arg251His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with autosomal dominant hereditary motor neuropathy and has been observed to segregate with disease in multiple families (PMID: 26392352, Invitae). ClinVar contains an entry for this variant (Variation ID: 197195). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg251 amino acid residue in DYNC1H1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30122514). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000623418 SCV000742400 uncertain significance Inborn genetic diseases 2017-04-18 criteria provided, single submitter clinical testing
GeneDx RCV000178163 SCV001769846 pathogenic not provided 2020-10-30 criteria provided, single submitter clinical testing Reported as likely pathogenic in an individual with hereditary motor neuropathy (HMN); however phenotypic details and segregation data were not provided (Antoniadi et al., 2015); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26392352, 30122514)

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