ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.4822G>A (p.Ala1608Thr) (rs138617999)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000713672 SCV000229885 uncertain significance not provided 2018-01-11 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000324886 SCV000461481 likely benign Emery-Dreifuss muscular dystrophy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000379472 SCV000461482 likely benign Cerebellar ataxia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000560151 SCV000649184 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1615 of the SYNE1 protein (p.Ala1615Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs138617999, ExAC 0.1%) but has not been reported in the literature in individuals with a SYNE1-related disease. ClinVar contains an entry for this variant (Variation ID: 197018). 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 threonine amino acid residue is also 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. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000177924 SCV000714054 likely benign not specified 2017-09-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000713672 SCV000844299 likely benign not provided 2019-03-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000177924 SCV001157718 uncertain significance not specified 2018-07-12 criteria provided, single submitter clinical testing The SYNE1 c.4843G>A; p.Ala1615Thr variant (rs138617999), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 197018). This variant is found in the non-Finnish European population with an overall allele frequency of 0.15% (195/126496 alleles) in the Genome Aggregation Database. The alanine at codon 1615 is weakly conserved and is found as a threonine in multiple mammalian species, and computational analyses (SIFT: tolerated, PolyPhen-2: benign) predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Ala1615Thr variant is uncertain at this time.

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