Submissions for variant NM_170707.4(LMNA):c.1072G>A (p.Glu358Lys) (rs60458016)

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Total submissions: 6

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000057227	SCV000331050	pathogenic	not provided	2016-10-04	criteria provided, single submitter	clinical testing
Invitae	RCV000470514	SCV000548856	pathogenic	Charcot-Marie-Tooth disease, type 2	2019-12-24	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid with lysine at codon 358 of the LMNA protein (p.Glu358Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (rs60458016, ExAC no frequency). This variant has been reported in several individuals affected with Emery-Dreifuss muscular dystrophy, infantile inflammatory myopathy, and dilated cardiomyopathy (PMID: 10939567, 20980393, 23183350, 24508248, 21632249). This variant has also been reported in individuals in the Leiden Open-Source Variation Database, and was reported to arise de novo in individuals affected with Emery-Dreifuss muscular dystrophy and limb girdle muscular dystrophy (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 14525). Experimental studies have shown that this missense change leads to mislocalization of the LMNA protein, with decreased nuclear rim staining and formation of intranuclear foci (PMID: 23427149, 11792809). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory,University of Chicago	RCV000502108	SCV000595623	pathogenic	Muscular dystrophy	2013-02-08	criteria provided, single submitter	clinical testing
OMIM	RCV000015622	SCV000035887	pathogenic	Emery-Dreifuss muscular dystrophy 2, autosomal dominant	2008-08-01	no assertion criteria provided	literature only
OMIM	RCV000015623	SCV000035888	pathogenic	Congenital muscular dystrophy, LMNA-related	2008-08-01	no assertion criteria provided	literature only
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000057227	SCV000088340	not provided	not provided		no assertion provided	not provided

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