Submissions for variant NM_000117.3(EMD):c.135dup (p.Arg46fs)

dbSNP: rs1557182301

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638214	SCV000759700	pathogenic	X-linked Emery-Dreifuss muscular dystrophy	2018-07-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EMD are known to be pathogenic (PMID: 24365856). This sequence change creates a premature translational stop signal (p.Arg46Alafs*15) in the EMD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EMD-related disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001553580	SCV001774481	likely pathogenic	Emery-Dreifuss muscular dystrophy	2021-07-29	criteria provided, single submitter	clinical testing	Variant summary: EMD c.135dupG (p.Arg46AlafsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 172063 control chromosomes (gnomAD). To our knowledge, no occurrence of c.135dupG in individuals affected with Emery-Dreifuss Muscular Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.