ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.16295G>A (p.Arg5432Gln) (rs200812806)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000270933 SCV000615577 uncertain significance not specified 2016-12-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725167 SCV000334597 uncertain significance not provided 2018-06-15 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765874 SCV000897272 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000725167 SCV000617095 uncertain significance not provided 2019-01-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SYNE1 gene. The R5361Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R5361Q variant is observed in 60/126702 (0.05%) alleles from individuals of European background (Lek et al., 2016). The R5361Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved; and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000309098 SCV000461117 uncertain significance Cerebellar ataxia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000363758 SCV000461118 uncertain significance Emery-Dreifuss muscular dystrophy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000765874 SCV000936412 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 5361 of the SYNE1 protein (p.Arg5361Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200812806, ExAC 0.06%). This variant has not been reported in the literature in individuals with SYNE1-related disease. ClinVar contains an entry for this variant (Variation ID: 282877). 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 glutamine 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 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.

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