ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.9148C>G (p.Leu3050Val) (rs117360770)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000179213 SCV000231423 likely benign not specified 2015-10-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000349953 SCV000461361 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.
Illumina Clinical Services Laboratory,Illumina RCV000388054 SCV000461362 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.
GeneDx RCV000179213 SCV000523963 likely benign not specified 2018-03-13 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.
Invitae RCV001089269 SCV000649226 likely benign Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000713694 SCV000844321 benign not provided 2018-10-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000179213 SCV000884633 uncertain significance not specified 2018-07-12 criteria provided, single submitter clinical testing The p.Leu3057Val variant (rs117360770) was reported in one patient with cerebellar ataxia, who also carried a frameshift mutation in the SYNE1 gene (Keogh, 2015), and further observed in one healthy control individual (Gonzalez-Garay, 2013). This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.3 percent in the European Non-Finnish population (identified on 369 out of 126,526 chromosomes, including 2 homozygotes), and has been reported to the ClinVar database (Variation ID: 198014). The leucine at position 3,057 is moderately conserved and computational analyses of the effects of the p.Leu3057Val variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Leu3057Val variant with certainty.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000713694 SCV001154946 likely benign not provided 2020-03-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.