ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.9715C>G (p.Gln3239Glu) (rs149901087)

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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 RCV000370965 SCV000334407 likely benign not specified 2017-04-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000391866 SCV000461345 benign Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000312113 SCV000461346 uncertain significance Spinocerebellar ataxia, autosomal recessive 8 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000766628 SCV000581805 uncertain significance not provided 2017-04-28 criteria provided, single submitter clinical testing The Q3246E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q3246E variant is observed in 12/11526 (0.1%) alleles from individuals of Latino background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This 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 conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with SYNE1-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Athena Diagnostics Inc RCV000766628 SCV000615697 likely benign not provided 2019-06-27 criteria provided, single submitter clinical testing
Invitae RCV001085001 SCV001015736 likely benign Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000370965 SCV001159650 uncertain significance not specified 2018-10-05 criteria provided, single submitter clinical testing The SYNE1: p.Gln3246Glu variant (rs149901087) has not been 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 a population frequency of 0.6 percent in the Ashkenazi Jewish population (identified on 62 out of 10,152 chromosomes) and has been reported to the ClinVar database (Variation ID: 282775). The glutamine at position 3246 is moderately conserved and computational analyses of the p.Gln3246Glu variant on protein structure and function provide conflicting results (SIFT: tolerated, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Gln3246Glu variant with certainty.

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