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
Genetic Services Laboratory, University of Chicago	RCV000145898	SCV000193035	pathogenic	Myopathy, centronuclear	2013-02-08	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
Invitae	RCV000554046	SCV000640223	pathogenic	Charcot-Marie-Tooth disease, dominant intermediate B	2019-09-29	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.
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV000626717	SCV000747420	pathogenic	Myopathy	2017-01-01	criteria provided, single submitter	clinical testing
OMIM	RCV000007705	SCV000027906	pathogenic	Myopathy, centronuclear, 1	2006-11-01	no assertion criteria provided	literature only

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