ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.4732C>T (p.Pro1578Ser) (rs199769508)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000397637 SCV000342491 uncertain significance not provided 2017-09-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778782 SCV000915152 uncertain significance Spinocerebellar ataxia, autosomal recessive 8 2018-10-23 criteria provided, single submitter clinical testing The SYNE1 c.4753C>T (p.Pro1585Ser) variant is a missense variant that has been reported in a compound heterozygous state with a frameshift variant in one individual affected with unexplained degenerative ataxia (Mademan et al. 2016). Control data are unavailable for the p.Pro1585Ser variant, which is reported at a frequency of 0.000404 in the European (non-Finnish) population of the Genome Aggregation Database. Immunohistochemistry analysis of muscle samples from the patient showed severely reduced SYNE1 staining (Mademan et al. 2016). Based on the limited evidence, the p.Pro1585Ser variant is classified as a variant of unknown significance but suspicious for pathogenicity for an autosomal recessive form of cerebellar ataxia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000792483 SCV000931785 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-09-10 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1585 of the SYNE1 protein (p.Pro1585Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs199769508, ExAC 0.04%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with cerebellar ataxia plus motor neuron disease (PMID: 27197992). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as p.Pro1578Ser in the literature. ClinVar contains an entry for this variant (Variation ID: 288391). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.
Athena Diagnostics Inc RCV000397637 SCV001145973 uncertain significance not provided 2019-01-15 criteria provided, single submitter clinical testing

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