ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1671GGA[5] (p.Glu562dup) (rs397517848)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041164 SCV000064855 uncertain significance not specified 2012-05-01 criteria provided, single submitter clinical testing The Glu562_Gly563insGlu variant (NEXN) has not been reported in the literature n or previously identified by our laboratory. This variant results in an in-frame duplication of Glutamine (Glu) within a stretch of 7 Glutamine residues in exon 13 of NEXN. A deletion of 2 of the 7 Glutamine residues has been identified by o ur laboratory in two individuals with cardiomyopathy. However, the NEXN gene has not been widely studied and therefore the types of variants causing disease are not yet well characterized. Additional information is needed to assess the clin ical significance of the Glu562_Gly563insGlu variant.
GeneDx RCV000767037 SCV000236151 uncertain significance not provided 2017-05-11 criteria provided, single submitter clinical testing The c.1680_1682dupGGA variant of uncertain significance in the NEXN gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1680_1682dupGGA variant results in an in-frame duplication of a single glutamic acid residue located within a region of glutamic acid repeats. Only one downstream non-frameshift variant in the NEXN gene has been reported in the Human Gene Mutation Database in association with DCM (Stenson et al., 2014); the majority of variants in the NEXN gene reported in HGMD are missense variants.
Ambry Genetics RCV000621511 SCV000737334 uncertain significance Cardiovascular phenotype 2017-12-16 criteria provided, single submitter clinical testing The c.1680_1682dupGGA variant (also known as p.E562dup), located in coding exon 12 of the NEXN gene, results from an in-frame duplication of GGA at nucleotide positions 1680 to 1682. This results in the duplication of a glutamic acid residue at codon 562. This amino acid position is not well conserved in available vertebrate species, and the number of glutamic acids in this glutamic acid tract is variable in other vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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