ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1609_1610insA (p.Leu537fs) (rs779350415)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725298 SCV000335814 uncertain significance not provided 2015-10-12 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000301273 SCV000712380 uncertain significance not specified 2016-07-28 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Leu537fs variant in NEXN has not been previously reported in individuals with cardiomyopa thy, but has been identified in 1/66208 European chromosomes by the Exome Aggreg ation Consortium (ExAC,; dbSNP rs779350415). This variant is predicted to cause a frameshift, which alters the protein?s amino ac id sequence beginning at position 537 and leads to a premature termination codon 7 amino acids downstream. Although the severe nature of this change increases t he likelihood that the variant is pathogenic, the NEXN gene has not been widely studied and the spectrum of variants leading to disease is not well-defined. Los s of NEXN function has been shown to cause DCM in zebrafish; however, it remains unclear if one or both copies of the gene need to be affected to cause disease (Hassel 2009, Wang 2010). In summary, while there is some suspicion for a pathog enic role, the clinical significance of the p.Leu537fs variant is uncertain.
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV001254746 SCV001430833 uncertain significance Long QT syndrome 2019-04-23 no assertion criteria provided research This variant has been identified as part of our research program. Refer to the 'condition' field for the phenotype of the proband identified with this variant. For further information please feel free to contact us.

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