ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.23260G>A (p.Val7754Ile) (rs150550013)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000322222 SCV000343088 uncertain significance not provided 2016-12-19 criteria provided, single submitter clinical testing
Invitae RCV000541902 SCV000649131 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2016-10-26 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 7683 of the SYNE1 protein (p.Val7683Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs150550013, ExAC 0.03%) 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The isoleucine 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000322222 SCV000884642 uncertain significance not provided 2017-09-29 criteria provided, single submitter clinical testing The p.Val7683Ile variant (rs150550013) has not been reported in the medical literature. The p.Val7683Ile variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.02% (identified in 56 out of 276,916 chromosomes), and is classified as a variant of uncertain significance in ClinVar (Variant ID: 288855). The valine at codon 7683 is weakly conserved considering 12 species (Alamut software v2.10.0), and computational analyses predict that this variant does not affect the structure/function of the SYNE1 protein (SIFT: tolerated, PolyPhen2: benign, MutationTaster: polymorphism). However, based on the available information, the clinical significance of the p.Val7683Ile variant cannot be determined with certainty.

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