Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000183676 | SCV000236145 | pathogenic | not provided | 2013-04-08 | criteria provided, single submitter | clinical testing | The c.461_464delACAA variant in the NEXN gene has not been reported as a disease-causing mutation to our knowledge. This variant causes a shift in reading frame starting at codon Asparagine 154, changing it to a Isoleucine, and creating a premature stop codon at position 17 of the new reading frame, denoted p.Asn154IlefsX17. This variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. However, there have been no truncating mutations in the NEXN gene reported to date. With the clinical and molecular information available at this time, we cannot definitively determine if c.461_464delACAA is a disease-causing mutation or a rare benign variant |
| Labcorp Genetics |
RCV001852365 | SCV002238369 | pathogenic | Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 | 2023-09-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 201937). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn154Ilefs*17) in the NEXN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEXN are known to be pathogenic (PMID: 32058062, 32814711, 32870709, 33949776). |
| Ambry Genetics | RCV002336468 | SCV002637762 | uncertain significance | Cardiovascular phenotype | 2023-12-04 | criteria provided, single submitter | clinical testing | The c.461_464delACAA variant, located in coding exon 5 of the NEXN gene, results from a deletion of 4 nucleotides at nucleotide positions 461 to 464, causing a translational frameshift with a predicted alternate stop codon (p.N154Ifs*17). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Although biallelic loss of function alterations in NEXN have been associated with autosomal recessive NEXN-related cardiomyopathy, haploinsufficiency for NEXN has not been clearly established as a mechanism of disease for autosomal dominant NEXN-related cardiomyopathy. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |