ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.1943G>A (p.Arg648Gln) (rs768605521)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756746 SCV000884650 uncertain significance not provided 2018-05-05 criteria provided, single submitter clinical testing The SYNE1 c.1964G>A; p.Arg655Gln variant (rs768605521), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.008% (identified on 21 out of 244,540 chromosomes). The arginine at position 655 is moderately conserved, considering 12 species, and computational analyses of the effects of the p.Arg655Gln variant on protein structure and function make conflicting predictions (SIFT: tolerated, PolyPhen-2: probably damaging). Based on the available information, the clinical significance of the p.Arg655Gln variant cannot be determined with certainty.
Invitae RCV001040021 SCV001203574 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 655 of the SYNE1 protein (p.Arg655Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs768605521, ExAC 0.03%). This variant has not been reported in the literature in individuals with SYNE1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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