Submissions for variant NM_001005361.3(DNM2):c.1880C>G (p.Pro627Arg)

dbSNP: rs587783598

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145910	SCV000193047	likely pathogenic	Centronuclear myopathy	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000235945	SCV000292784	pathogenic	not provided	2016-08-17	criteria provided, single submitter	clinical testing	The P627R mutation in the DNM2 gene has been reported previously in an affected mother and daughter who had childhood-onset centronuclear myopathy (CNM). They both had walking difficulties, reduced vital capacity, diffuse muscle weakness, and facial weakness (Bohm et al., 2012). Additionally, another missense mutation at the same position (P627H) and multiple missense mutations in nearby residues (A618T/D, S619L/W, L621P) have been reported in the Human Gene Mutation Database in association with CNM (Stenson et al., 2014). The P627R mutation is a non-conservative amino acid substitution that alters a highly conserved residue predicted to be within the linker domain between the pleckstrin homology (PH) domain and GTPase effector domain (GED) (Bohm et al., 2012). Therefore, the presence of the P672R mutation is consistent with a diagnosis of centronuclear myopathy
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV002286706	SCV002577423	pathogenic	Autosomal dominant centronuclear myopathy	2022-09-21	criteria provided, single submitter	clinical testing	PM1, PM2, PM5, PP3, PP5
Inherited Neuropathy Consortium Ii, University Of Miami	RCV003447118	SCV004174751	uncertain significance	Charcot-Marie-Tooth disease dominant intermediate B	2016-01-06	no assertion criteria provided	literature only