Submissions for variant NM_144573.4(NEXN):c.989AAG[2] (p.Glu332del)

dbSNP: rs727505124

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156581	SCV000206300	uncertain significance	not specified	2015-08-12	criteria provided, single submitter	clinical testing	The p.Glu332del variant in NEXN has been identified by our laboratory in 1 Cauca sian adult with HCM. This variant has also been identified in 12/16490 of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadin stitute.org; dbSNP rs727505124). This variant is a deletion of 1 amino acid at p osition 332 and is not predicted to alter the protein reading-frame. It is uncle ar if this deletion will impact the protein. In summary, the clinical significan ce of the p.Glu332del variant is uncertain.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769820	SCV000901246	uncertain significance	Cardiomyopathy	2017-10-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001699134	SCV001985752	uncertain significance	not provided	2019-06-07	criteria provided, single submitter	clinical testing	Identified in a patient with HCM in the published literature (Haskell et al., 2017; reported as c.987_989delAGA due to the use of alternate nomenclature); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-frame deletion of 1 amino acid in a non-repeat region; This variant is associated with the following publications: (PMID: 28611029)
Ambry Genetics	RCV002381502	SCV002690109	likely benign	Cardiovascular phenotype	2019-10-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV002484953	SCV002787927	uncertain significance	Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20	2021-08-30	criteria provided, single submitter	clinical testing
Invitae	RCV002484953	SCV003237745	uncertain significance	Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20	2021-12-24	criteria provided, single submitter	clinical testing	This variant, c.995_997del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Glu332del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs751883872, gnomAD 0.06%). This variant has been observed in individual(s) with cardiomyopathy (PMID: 28611029). This variant is also known as c.987_989delAGA (p.Ala329_Glu330delinsAla). ClinVar contains an entry for this variant (Variation ID: 179783). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Clinical Genetics, Academic Medical Center	RCV001699134	SCV001924053	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699134	SCV001954730	uncertain significance	not provided		no assertion criteria provided	clinical testing