Submissions for variant NM_001005361.3(DNM2):c.1856C>T (p.Ser619Leu)

dbSNP: rs121909095

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145908	SCV000193045	pathogenic	Centronuclear myopathy	2013-02-08	criteria provided, single submitter	clinical testing
Invitae	RCV000544279	SCV000640231	pathogenic	Charcot-Marie-Tooth disease dominant intermediate B	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 619 of the DNM2 protein (p.Ser619Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with centronuclear myopathy and is associated with severe neonatal hypotonia (PMID: 17932957, 20227276, 22396310). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 7285). 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. Experimental studies have shown that this missense change affects DNM2 function (PMID: 20700106, 23338057, 24135484, 26199319). This variant disrupts the p.Ser619 amino acid residue in DNM2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17932957, 20700106, 22396310, 25957634). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
NeuroMeGen, Hospital Clinico Santiago de Compostela	RCV000754751	SCV000882642	likely pathogenic	Autosomal dominant centronuclear myopathy	2018-10-08	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000754751	SCV001426504	pathogenic	Autosomal dominant centronuclear myopathy		criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002504764	SCV002816335	pathogenic	Charcot-Marie-Tooth disease dominant intermediate B; Autosomal dominant centronuclear myopathy; Fetal akinesia-cerebral and retinal hemorrhage syndrome	2021-08-20	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 (Pr. Bezieau's lab), CHU de Nantes	RCV000656268	SCV000778232	pathogenic	not provided	2016-12-12	no assertion criteria provided	clinical testing
Inherited Neuropathy Consortium Ii, University Of Miami	RCV000544279	SCV004174699	uncertain significance	Charcot-Marie-Tooth disease dominant intermediate B	2016-01-06	no assertion criteria provided	literature only