ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.17347G>C (p.Glu5783Gln) (rs754105532)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535433 SCV000649065 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-03-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 5712 of the SYNE1 protein (p.Glu5712Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant also falls at the first nucleotide of exon 91 of the SYNE1 coding sequence. This variant is present in population databases (rs754105532, ExAC 0.002%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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