ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.1572_1574delAGA (rs764505909)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656930 SCV000225714 uncertain significance not provided 2014-11-22 criteria provided, single submitter clinical testing
GeneDx RCV000656930 SCV000236114 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEXN gene. The c.1582_1584delGAA variant was reported as homozygous in a one month old and two siblings with DCM and a family history of consanguinity (poster/oral abstract: Zuhair et al., 2013). The c.1582_1584delGAA variant is observed in 43/276274 (0.016%) alleles from individuals of multiple ethnic backgrounds in large population cohorts (Lek et al., 2016). This variant results in the in-frame deletion of a single glutamic acid, denoted p.E528del. This residue is located within a glutamic acid four-repeat sequence that is not conserved across species. Finally, this variant is not expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000183645 SCV000272211 uncertain significance not specified 2015-06-12 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Glu528del variant has been identified in 2 consanguineous families of Middle Eastern anc estry as homozygous in 5 affected siblings (Conference abstract by Al-Hassnan 20 13, LMM unpublished data). This variant has also been identified as heterozygous in 14/65856 European chromosomes by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org). This variant is a deletion of 1 amino acid at posi tion 528 from a string of 4 glutamic acids. It is unclear if this deletion will impact the protein. In summary, while there is some suspicion for a pathogenic r ole, the clinical significance of the p.Glu528del variant is uncertain.
Invitae RCV000647277 SCV000769066 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2019-09-28 criteria provided, single submitter clinical testing This variant, c.1582_1584delGAA, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Glu528del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs770868024, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in a family affected with dilated cardiomyopathy (http://www.sciencedirect.com/science/article/pii/S1016731513002133). ClinVar contains an entry for this variant (Variation ID: 194130). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769827 SCV000901253 uncertain significance Cardiomyopathy 2017-08-14 criteria provided, single submitter clinical testing
Klaassen Lab,Charite University Medicine Berlin RCV000853115 SCV000995826 uncertain significance Primary dilated cardiomyopathy 2019-07-03 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000656930 SCV001147320 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing

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