ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.1174C>T (p.Arg392Ter) (rs750076188)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000222720 SCV000272207 uncertain significance not specified 2015-04-23 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg392X v ariant in NEXN has not been previously reported in individuals with cardiomyopat hy, but has been identified in 1/64806 of European chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 392, which is predicted to l ead to a truncated or absent protein. Although the severe nature of this change increases the likelihood that the variant is pathogenic, the NEXN gene has not b een widely studied and the spectrum of variants leading to disease is not well-d efined. Loss of NEXN function has been shown to cause DCM in zebrafish (Hassel 2 009, Wang 2010) and loss of function variants have been identified in individual s with a range of cardiomyopathies (LMM unpublished data); however, it remains u nclear if one or both copies of the gene need to be affected to cause disease. I n summary, while there is some suspicion for a pathogenic role, the clinical sig nificance of the p.Arg392X variant is uncertain.
Invitae RCV000820993 SCV000961732 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2018-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg392*) in the NEXN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs750076188, ExAC 0.002%). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 25163546). ClinVar contains an entry for this variant (Variation ID: 229051). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NEXN cause disease. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.