ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.16984C>T (p.Arg5662Cys)

dbSNP: rs145899734
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000710244 SCV000337116 uncertain significance not provided 2016-12-23 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000266512 SCV000461105 uncertain significance Autosomal recessive ataxia, Beauce type 2018-01-12 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 Laboratory Services, Illumina RCV000321614 SCV000461106 benign Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-01-12 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 RCV000710244 SCV000589363 uncertain significance not provided 2023-08-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27178001, 27086870)
Athena Diagnostics Inc RCV000710244 SCV000615580 likely benign not provided 2020-07-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000710244 SCV001335157 likely benign not provided 2023-06-01 criteria provided, single submitter clinical testing SYNE1: BP4
Johns Hopkins Genomics, Johns Hopkins University RCV000266512 SCV001441543 uncertain significance Autosomal recessive ataxia, Beauce type 2020-11-03 criteria provided, single submitter clinical testing
Baylor Genetics RCV001331537 SCV001523598 uncertain significance Arthrogryposis multiplex congenita 3, myogenic type 2020-06-08 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV001362101 SCV001558103 uncertain significance Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 5591 of the SYNE1 protein (p.Arg5591Cys). This variant is present in population databases (rs145899734, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 284474). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002518932 SCV003621811 uncertain significance Inborn genetic diseases 2021-08-16 criteria provided, single submitter clinical testing The c.16771C>T (p.R5591C) alteration is located in exon 88 (coding exon 87) of the SYNE1 gene. This alteration results from a C to T substitution at nucleotide position 16771, causing the arginine (R) at amino acid position 5591 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity Omics RCV000710244 SCV003824722 uncertain significance not provided 2024-01-05 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV003417894 SCV004118246 uncertain significance SYNE1-related condition 2023-03-16 criteria provided, single submitter clinical testing The SYNE1 c.16771C>T variant is predicted to result in the amino acid substitution p.Arg5591Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.10% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-152631566-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252119 SCV001427868 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000710244 SCV001743028 uncertain significance not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000710244 SCV001799058 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000710244 SCV001972360 uncertain significance not provided no assertion criteria provided 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.