ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.1102G>A (p.Glu368Lys) (rs121909092)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626717 SCV000747420 pathogenic Muscular Diseases 2017-01-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725988 SCV000341047 pathogenic not provided 2016-05-12 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000145898 SCV000193035 pathogenic Myopathy, centronuclear 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000554046 SCV000640223 pathogenic Charcot-Marie-Tooth disease, dominant intermediate B 2018-09-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 368 of the DNM2 protein (p.Glu368Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121909092, ExAC 0.006%). This variant has been reported repeatedly in the literature in individuals affected with autosomal dominant centronuclear myopathy (PMID: 22613877, 25501959, 25262827, 20927630, 22396310, 23338057, 20227276, 17008356, 24465259, 21221624, 19130742).  It is considered one of the most common mutations causing this disorder and has been shown to arise de novo in numerous affected individuals (PMID: 16227997, 25957634, 23338057, 26273216, 22396310, 23394783).  ClinVar contains an entry for this variant (Variation ID: 7282) Experimental studies have shown that this variant causes an increase in GTPase activity of the dynamin-2 protein along and formation of oligomers that are resistant to disassembly (PMID: 20529869). Additionally this variant has been shown to have a dominant negative effect on dynamin-2 protein function (PMID: 26199319, 21762456). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007705 SCV000027906 pathogenic Myopathy, centronuclear, 1 2006-11-01 no assertion criteria provided literature only

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