ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.9091A>G (p.Arg3031Gly) (rs144643941)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726953 SCV000536356 uncertain significance not provided 2017-01-25 criteria provided, single submitter clinical testing The R3038G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R3038G variant is observed in 10/10354 (0.1%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. However, this 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. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Genetic Services Laboratory, University of Chicago RCV000435987 SCV000597342 uncertain significance not specified 2016-10-10 criteria provided, single submitter clinical testing
Invitae RCV000532681 SCV000649225 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 3038 of the SYNE1 protein (p.Arg3038Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs144643941, ExAC 0.1%) but has not been reported in the literature in individuals with a SYNE1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726953 SCV000704417 uncertain significance not provided 2017-01-04 criteria provided, single submitter clinical testing

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