ClinVar Miner

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

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512659 SCV000608712 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414974 SCV000492853 likely pathogenic Muscular Diseases; Pes cavus; Hammertoe; Distal lower limb amyotrophy 2015-05-11 criteria provided, single submitter clinical testing
Invitae RCV000649558 SCV000771387 uncertain significance Charcot-Marie-Tooth disease, axonal, type 2O 2018-07-27 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 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. 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.

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