ClinVar Miner

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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