ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1788T>G (p.Ser596Arg) (rs199738750)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041167 SCV000064858 uncertain significance not specified 2015-04-08 criteria provided, single submitter clinical testing The p.Ser596Arg variant in NEXN has been identified by our laboratory in 1 Cauca sian infant with DCM. This variant has also been identified in 28/66528 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu; dbSNP rs199738750). Computational prediction tools and conservation anal ysis do not provide strong support for or against an impact to the protein. In s ummary, the clinical significance of the p.Ser596Arg variant is uncertain.
Invitae RCV000232351 SCV000291368 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2019-12-15 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 596 of the NEXN protein (p.Ser596Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs199738750, ExAC 0.04%). This variant has not been reported in the literature in individuals with a NEXN-related disease. ClinVar contains an entry for this variant (Variation ID: 47897). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on NEXN function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000157391 SCV000900180 uncertain significance Cardiomyopathy 2017-01-10 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994030 SCV001147321 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282086 SCV001160307 uncertain significance none provided 2020-03-12 criteria provided, single submitter clinical testing The NEXN c.1788T>G; p.Ser596Arg variant (rs199738750) is reported in the literature in a family affected with dilated cardiomyopathy, but without a clear association with disease (Kumar 2018). This variant is reported in ClinVar (Variation ID: 47897), and is found in the general population with an overall allele frequency of 0.02% (69/280486 alleles) in the Genome Aggregation Database. The serine at codon 596 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Ser596Arg variant is uncertain at this time. References: Kumar D and Elliott P. Cardiovascular Genetics and Genomics: Principles and Clinical Practice. Springer 2018 Jan 17; 341-2.
GeneDx RCV000994030 SCV001758828 likely benign not provided 2020-11-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30847666)
Blueprint Genetics RCV000157391 SCV000207129 uncertain significance Cardiomyopathy 2014-10-28 no assertion criteria provided clinical testing

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