ClinVar Miner

Submissions for variant NM_001005361.3(DNM2):c.1739T>C (p.Met580Thr)

dbSNP: rs1269225724
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001542797 SCV003442703 pathogenic Charcot-Marie-Tooth disease dominant intermediate B 2022-10-24 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 580 of the DNM2 protein (p.Met580Thr). This missense change has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 22091729). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNM2 protein function. ClinVar contains an entry for this variant (Variation ID: 637072).
GeneDx RCV003128698 SCV003805294 pathogenic not provided 2022-09-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); 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: 34758253, 33979205, Renwick2016[Review], 22091729, 28251916)
Inherited Neuropathy Consortium RCV000789090 SCV000928441 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Genomics England Pilot Project, Genomics England RCV001542797 SCV001760433 pathogenic Charcot-Marie-Tooth disease dominant intermediate B no assertion criteria provided clinical testing
Inherited Neuropathy Consortium Ii, University Of Miami RCV001542797 SCV004174757 uncertain significance Charcot-Marie-Tooth disease dominant intermediate B 2016-01-06 no assertion criteria provided literature only

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