ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.13435C>T (p.Arg4479Cys)

gnomAD frequency: 0.00001  dbSNP: rs778601377
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000726500 SCV000345085 uncertain significance not provided 2016-09-23 criteria provided, single submitter clinical testing
GeneDx RCV000726500 SCV000536596 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SYNE1 gene. The R4408C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R4408C variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R4408C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to 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.
Invitae RCV000799265 SCV000938919 uncertain significance Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2022-04-01 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 4408 of the SYNE1 protein (p.Arg4408Cys). This variant is present in population databases (rs778601377, gnomAD 0.006%). ClinVar contains an entry for this variant (Variation ID: 290514). 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. 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.
Revvity Omics, Revvity RCV000726500 SCV003822800 uncertain significance not provided 2022-11-18 criteria provided, single submitter clinical testing

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