ClinVar Miner

Submissions for variant NM_001190716.2(DNM2):c.1072G>A (p.Gly358Arg) (rs267606772)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203266 SCV000256740 likely pathogenic Charcot-Marie-Tooth disease, dominant intermediate B 2014-09-25 criteria provided, single submitter research
GeneDx RCV000369987 SCV000329751 likely pathogenic not provided 2017-01-11 criteria provided, single submitter clinical testing The G358R variant in the DNM2 gene has been reported previously in association with Charcot-Marie-Tooth disease (Gallardo et al., 2008; Yamamoto et al., 2014). Functional studies suggest that the G358R variant impacts myelination and clathrin-mediated endocytosis (Sidiropoulos et al., 2012). The G358R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G358R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, G358R is considered to be a pathogenic variant.
Athena Diagnostics Inc RCV000369987 SCV000613145 pathogenic not provided 2017-04-12 criteria provided, single submitter clinical testing
Invitae RCV000203266 SCV001222989 likely pathogenic Charcot-Marie-Tooth disease, dominant intermediate B 2020-01-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 358 of the DNM2 protein (p.Gly358Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Charcot-Marie-Tooth disease in a family (PMID: 18560793). ClinVar contains an entry for this variant (Variation ID: 7287). This variant has been reported to affect DNM2 protein function (PMID: 22451505, 22096584, 28357347). 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.
OMIM RCV000007710 SCV000027911 pathogenic Charcot-Marie-Tooth disease, type 2M 2009-07-01 no assertion criteria provided literature only

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