Submissions for variant NM_182961.4(SYNE1):c.25856T>C (p.Leu8619Pro)

gnomAD frequency: 0.00178  dbSNP: rs139834542

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000713653	SCV000333860	uncertain significance	not provided	2018-06-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000304397	SCV000460871	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 Laboratory Services, Illumina	RCV000363295	SCV000460872	uncertain significance	Autosomal recessive ataxia, Beauce type	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	RCV000713653	SCV000525164	likely benign	not provided	2020-08-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080413	SCV000649154	likely benign	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2025-01-30	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000364185	SCV000844280	likely benign	not specified	2021-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000713653	SCV000884648	uncertain significance	not provided	2018-05-05	criteria provided, single submitter	clinical testing	The SYNE1 c.25712T>C; p.Leu8571Pro variant (rs139834542, ClinVar variant ID 282403), to our knowledge, is not 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 non-Finnish European population frequency of 0.2% (identified on 315 out of 126,708 chromosomes, including one homozygote). The leucine at position 8571 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Leu8571Pro variant on protein structure and function predict a deleterious effect (SIFT: damaging, PolyPhen-2: probably damaging). Based on the available information, the clinical significance of the p.Leu8571Pro variant cannot be determined with certainty.
CeGaT Center for Human Genetics Tuebingen	RCV000713653	SCV001502042	likely benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	SYNE1: BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV000713653	SCV001714199	uncertain significance	not provided	2023-06-16	criteria provided, single submitter	clinical testing	BS1
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000713653	SCV001740243	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000713653	SCV001931345	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000713653	SCV001970050	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004535281	SCV004747504	likely benign	SYNE1-related disorder	2024-07-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).