ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.25381G>A (p.Glu8461Lys) (rs119103248)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000713651 SCV000226187 uncertain significance not provided 2018-06-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000329983 SCV000460877 likely benign Cerebellar ataxia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000389137 SCV000460878 likely benign Emery-Dreifuss muscular dystrophy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000535163 SCV000649148 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 8413 of the SYNE1 protein (p.Glu8413Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs119103248, ExAC 0.2%). This variant has been reported in an individual affected with Emery–Dreifuss muscular dystrophy (EDMD), however, experimental studies found no functional difference between this variant and the wild-type protein (PMID: 17761684). ClinVar contains an entry for this variant (Variation ID: 2334). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function or cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000713651 SCV000844278 uncertain significance not provided 2017-10-23 criteria provided, single submitter clinical testing
Mendelics RCV000987800 SCV001137256 uncertain significance Spinocerebellar ataxia, autosomal recessive 8 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000713651 SCV001154908 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002110 SCV001159957 uncertain significance not specified 2018-09-28 criteria provided, single submitter clinical testing The SYNE1 c.25237G>A; p.Glu8413Lys variant (rs119103248), also reported as c.2132G>A; p.Glu646Lys for a shorter alternate transcript by Zhang et al. (2007), was identified in an individual with Emery-Dreifuss Muscular Dystrophy-like symptoms; however, it has not been demonstrated to be disease-causing (Zhang 2007). This variant is reported in ClinVar (Variation ID: 2334) and is found in the Latino population with an overall allele frequency of 0.16% (55/34420 alleles) in the Genome Aggregation Database. The glutamate at codon 8413 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Glu8413Lys variant is uncertain at this time. References: Zhang Q et al. Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet. 2007 Dec 1;16(23):2816-33.
OMIM RCV000002424 SCV000022582 pathogenic Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2007-12-01 no assertion criteria provided literature only

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.