ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.17332A>G (p.Ile5778Val) (rs762422242)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000813021 SCV000953354 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-01-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 5707 of the SYNE1 protein (p.Ile5707Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs762422242, ExAC 0.009%). This variant has not been reported in the literature in individuals with SYNE1-related disease. 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.
Integrated Genetics/Laboratory Corporation of America RCV001193566 SCV001362477 uncertain significance not specified 2019-08-15 criteria provided, single submitter clinical testing Variant summary: SYNE1 c.17119A>G (p.Ile5707Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251476 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.17119A>G in individuals affected with Emery-Dreifuss muscular dystrophy 4, autosomal dominant and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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