Submissions for variant NM_182961.4(SYNE1):c.14501G>A (p.Arg4834Gln)

gnomAD frequency: 0.00040  dbSNP: rs141883764

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000713603	SCV000339469	uncertain significance	not provided	2016-02-11	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000713603	SCV000844228	uncertain significance	not provided	2023-10-27	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 predict that this variant is not damaging.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000807457	SCV000947510	uncertain significance	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2022-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 4763 of the SYNE1 protein (p.Arg4763Gln). This variant is present in population databases (rs141883764, gnomAD 0.09%). 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: 286148). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine 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.
GeneDx	RCV000713603	SCV002099711	uncertain significance	not provided	2025-02-05	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002519212	SCV003735653	uncertain significance	Inborn genetic diseases	2021-08-02	criteria provided, single submitter	clinical testing	The c.14288G>A (p.R4763Q) alteration is located in exon 77 (coding exon 76) of the SYNE1 gene. This alteration results from a G to A substitution at nucleotide position 14288, causing the arginine (R) at amino acid position 4763 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000713603	SCV003824691	uncertain significance	not provided	2022-04-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004535361	SCV004120251	uncertain significance	SYNE1-related disorder	2023-06-07	criteria provided, single submitter	clinical testing	The SYNE1 c.14288G>A variant is predicted to result in the amino acid substitution p.Arg4763Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.084% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-152651319-C-T), which is more common than expected for a disease-causing variant. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.