ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.1820_1822del (p.Gly607del) (rs876657928)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000220963 SCV000272212 uncertain significance not specified 2015-10-01 criteria provided, single submitter clinical testing The p.Gly607del variant in NEXN has not been previously reported in individuals with cardiomyopathy but has been identified in 3/66474 European chromosomes by t he Exome Aggregation Consortium (ExAC, This var iant is a deletion of 1 amino acid at position 607. It is unclear if this deleti on will impact the protein. In summary, the clinical significance of the p.Gly60 7del variant is uncertain.
GeneDx RCV000766520 SCV000616808 uncertain significance not provided 2017-07-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEXN gene. The c.1820_1822delGAG variant has not been published as pathogenic or been reported as benign to our knowledge. The c.1820_1822delGAG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1820_1822delGAG variant results in an in-frame deletion of a Glycine residue at codon 607, denoted p.Gly607del, and does not result in a shift in the reading frame or a premature stop codon. No nearby in-frame deletions in the NEXN gene have been reported in the Human Gene Mutation Database (HGMD) in association with cardiomyopathy, and the majority of variants in the NEXN gene reported in HGMD are missense variants (Stenson et al., 2014). However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV001069606 SCV001234785 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-02-11 criteria provided, single submitter clinical testing This variant, c.1820_1822del, results in the deletion of 1 amino acid(s) of the NEXN protein (p.Gly607del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs774370743, ExAC 0.005%). This variant has not been reported in the literature in individuals with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 229055). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) 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.
Ambry Genetics RCV001267104 SCV001445285 uncertain significance Inborn genetic diseases 2018-02-14 criteria provided, single submitter clinical testing

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