Submissions for variant NM_182961.4(SYNE1):c.16538G>A (p.Arg5513Lys)

gnomAD frequency: 0.00125  dbSNP: rs138745849

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000279360	SCV000338118	likely benign	not specified	2016-11-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000278107	SCV000461111	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.
Illumina Laboratory Services, Illumina	RCV000352181	SCV000461112	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.
GeneDx	RCV001705421	SCV000527436	likely benign	not provided	2021-03-12	criteria provided, single submitter	clinical testing
Invitae	RCV000543262	SCV000649057	likely benign	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2024-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519174	SCV003748204	uncertain significance	Inborn genetic diseases	2021-11-12	criteria provided, single submitter	clinical testing	The c.16325G>A (p.R5442K) alteration is located in exon 85 (coding exon 84) of the SYNE1 gene. This alteration results from a G to A substitution at nucleotide position 16325, causing the arginine (R) at amino acid position 5442 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003947890	SCV004764531	likely benign	SYNE1-related condition	2019-10-28	criteria provided, single submitter	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).