Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145898 | SCV000193035 | pathogenic | Myopathy, centronuclear | 2013-02-08 | criteria provided, single submitter | clinical testing | |
EGL Genetic 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, |
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 |