Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000145908 | SCV000193045 | pathogenic | Myopathy, centronuclear | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000544279 | SCV000640231 | pathogenic | Charcot-Marie-Tooth disease, dominant intermediate B | 2019-10-21 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 619 of the DNM2 protein (p.Ser619Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (rs121909095, ExAC no frequency). This variant has been reported in several families affected with centronuclear myopathy and is associated with severe neonatal hypotonia (PMID: 22396310). This variant has also been shown to arise de novo in multiple individuals affected with early-onset centronuclear myopathy (PMID: 17932957, 20227276). ClinVar contains an entry for this variant (Variation ID: 7285). A different missense substitution at this codon (p.Ser619Trp) has been determined to be pathogenic (PMID: 22396310, 25957634, 17932957, 20700106). This suggests that the serine residue is critical for DNM2 protein function and that other missense substitutions at this position may also be pathogenic. Experimental studies have shown that this missense change alters DNM2 protein structure and function, and leads to pathological changes in muscle and severe motor deficits in model systems (PMID: 20700106, 23338057, 26199319, 24135484). For these reasons, this variant has been classified as Pathogenic. |
Neuro |
RCV000754751 | SCV000882642 | likely pathogenic | Myopathy, centronuclear, 1 | 2018-10-08 | criteria provided, single submitter | clinical testing | |
Centogene AG - |
RCV000754751 | SCV001426504 | pathogenic | Myopathy, centronuclear, 1 | criteria provided, single submitter | clinical testing | ||
OMIM | RCV000007708 | SCV000027909 | pathogenic | Severe X-linked myotubular myopathy | 2007-12-01 | no assertion criteria provided | literature only | |
Laboratory of Molecular Genetics |
RCV000656268 | SCV000778232 | pathogenic | not provided | 2016-12-12 | no assertion criteria provided | clinical testing |