ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1415C>G (p.Ala472Gly)

gnomAD frequency: 0.00001  dbSNP: rs539665448
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
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 RCV000222980 SCV000272210 uncertain significance not specified 2015-04-01 criteria provided, single submitter clinical testing The p.Ala472Gly variant in NEXN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/11546 of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Comput ational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ala472Gly variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000466479 SCV000549239 uncertain significance Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 472 of the NEXN protein (p.Ala472Gly). This variant is present in population databases (rs539665448, gnomAD 0.03%). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 28798025). ClinVar contains an entry for this variant (Variation ID: 229054). 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: "Possibly 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.
Ambry Genetics RCV002390583 SCV002699708 uncertain significance Cardiovascular phenotype 2022-06-01 criteria provided, single submitter clinical testing The p.A472G variant (also known as c.1415C>G), located in coding exon 10 of the NEXN gene, results from a C to G substitution at nucleotide position 1415. The alanine at codon 472 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a left ventricular non-compaction (LVNC) cohort; however, clinical details were limited (Miszalski-Jamka K et al. Circ Cardiovasc Genet, 2017 Aug;10:[ePub ahead of print]). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000466479 SCV002782787 uncertain significance Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 2021-10-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV004791333 SCV005409252 uncertain significance not provided 2024-06-13 criteria provided, single submitter clinical testing BP4

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.