Submissions for variant NM_182961.4(SYNE1):c.12970C>T (p.Arg4324Cys)

gnomAD frequency: 0.00034  dbSNP: rs142258643

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000274125	SCV000337087	uncertain significance	not provided	2015-11-02	criteria provided, single submitter	clinical testing
Invitae	RCV001228711	SCV001401126	uncertain significance	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2022-08-23	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: 284455). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is present in population databases (rs142258643, gnomAD 0.1%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 4253 of the SYNE1 protein (p.Arg4253Cys).
GeneDx	RCV000274125	SCV001788901	uncertain significance	not provided	2022-04-11	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
Ambry Genetics	RCV002519151	SCV003630415	uncertain significance	Inborn genetic diseases	2021-08-12	criteria provided, single submitter	clinical testing	The c.12757C>T (p.R4253C) alteration is located in exon 77 (coding exon 76) of the SYNE1 gene. This alteration results from a C to T substitution at nucleotide position 12757, causing the arginine (R) at amino acid position 4253 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000274125	SCV003822746	uncertain significance	not provided	2021-11-16	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000274125	SCV004229233	uncertain significance	not provided	2023-08-11	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function.