Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular 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. |
| Gene |
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 (p.E562DUP) alteration is located in exon 13 (coding exon 12) of the NEXN gene. The alteration consists of an in-frame duplication of 3 nucleotides from position 1680 to 1682, resulting in the duplication of 1 residue. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002483027 | SCV002783921 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2021-08-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002483027 | SCV003448765 | uncertain significance | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2022-07-08 | criteria provided, single submitter | clinical testing | This variant, c.1680_1682dup, results in the insertion of 1 amino acid(s) of the NEXN protein (p.Glu562dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs397517849, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 47894). 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. |