ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.2026_*1del (rs794729094)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183688 SCV000236157 uncertain significance not specified 2014-10-24 criteria provided, single submitter clinical testing Although rare, mutations in the NEXN gene have been reported in association with autosomal dominant familial HCM and DCM (Wang H et al., 2010; Hassel D et al., 2009). The c.2026_2029delTAAT variant in the NEXN gene has not been published as a mutation or as a benign polymorphism to our knowledge. This mutation causes a shift in reading frame starting at codon Stop 676, changing it to a Histidine, which results in deletion of the normal stop codon and extension of the normal protein by 8 amino acid residues, denoted p.Ter676HisextX8. To date, only missense mutations and one in-frame deletion have been reported in NEXN in association with cardiomyopathy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000183688 SCV000713662 uncertain significance not specified 2017-09-11 criteria provided, single submitter clinical testing The p.X676HisextX9 variant in NEXN has not been previously reported in individua ls with cardiomyopathy but has been identified in 13/34248 of Latino chromosomes by the Genome Aggregation Database (gnomAD,; d bSNP rs794729094). This variant deletes the stop codon, replaces it with a Histi dine and extends the protein by 8 amino acids. The impact of this change on prot ein function is unknown. NEXN variants have been described in individuals with D CM and HCM but they are rare and overall poorly studied. In summary, the clinica l significance of the p.X676HisextX9 variant is uncertain.
Invitae RCV001043340 SCV001207076 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-10-07 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the NEXN gene (p.*676Hisext*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last amino acid of the NEXN protein and extend the protein by an additional 8 amino acids. This variant is present in population databases (rs764404383, ExAC 0.009%). This variant has not been reported in the literature in individuals with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 201946). 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.

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