ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1190G>A (p.Arg397Gln)

gnomAD frequency: 0.00007  dbSNP: rs201806320
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000215086 SCV000272208 uncertain significance not specified 2015-07-02 criteria provided, single submitter clinical testing The p.Arg397Gln variant in NEXN has not been previously reported in individuals with cardiomyopathy, but has been identified in 4/15976 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201806320). Computational prediction tools and conservation analysis do not p rovide strong support for or against an impact to the protein. In summary, the c linical significance of the p.Arg397Gln variant is uncertain.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769823 SCV000901249 uncertain significance Cardiomyopathy 2017-02-28 criteria provided, single submitter clinical testing
Invitae RCV001853472 SCV002272715 uncertain significance Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 2022-05-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 397 of the NEXN protein (p.Arg397Gln). This variant is present in population databases (rs201806320, gnomAD 0.02%). 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: 229052). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV002288842 SCV002578280 uncertain significance not provided 2022-04-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV002338685 SCV002640823 uncertain significance Cardiovascular phenotype 2023-03-20 criteria provided, single submitter clinical testing The p.R397Q variant (also known as c.1190G>A), located in coding exon 9 of the NEXN gene, results from a G to A substitution at nucleotide position 1190. The arginine at codon 397 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001853472 SCV002790506 uncertain significance Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 2021-09-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.