Submissions for variant NM_182961.4(SYNE1):c.17140C>T (p.Arg5714Trp)

gnomAD frequency: 0.00004  dbSNP: rs202171698

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000396416	SCV000345322	uncertain significance	not provided	2016-09-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000366354	SCV000461101	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000271813	SCV000461102	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.
Athena Diagnostics	RCV000396416	SCV002771365	uncertain significance	not provided	2021-07-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002519345	SCV003313053	uncertain significance	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2022-07-26	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 290710). This missense change has been observed in individuals with clinical features of spinocerebellar ataxia (PMID: 31692161; Invitae). This variant is present in population databases (rs202171698, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 5643 of the SYNE1 protein (p.Arg5643Trp).