ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.15608A>G (p.Glu5203Gly)

gnomAD frequency: 0.00003  dbSNP: rs375432465
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521653 SCV000621974 uncertain significance not provided 2017-11-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SYNE1 gene. The E5132G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E5132G variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The E5132G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001315863 SCV001506457 uncertain significance Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2020-03-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 5132 of the SYNE1 protein (p.Glu5132Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs375432465, ExAC 0.001%). This variant has not been reported in the literature in individuals with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 453112). 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, 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.
Revvity Omics, Revvity RCV000521653 SCV003825272 uncertain significance not provided 2021-05-17 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.