Submissions for variant NM_182961.4(SYNE1):c.9655G>A (p.Val3219Ile)

gnomAD frequency: 0.00132  dbSNP: rs140927945

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000713696	SCV000344689	uncertain significance	not provided	2018-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000713696	SCV000589856	uncertain significance	not provided	2018-11-13	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the SYNE1 gene. The V3226I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V3226I variant is observed in 34/10238 (0.3%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V3226I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics Inc	RCV000713696	SCV000844323	likely benign	not provided	2018-12-21	criteria provided, single submitter	clinical testing
Invitae	RCV001079193	SCV001005075	likely benign	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2024-01-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000713696	SCV004010622	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	SYNE1: BS1
PreventionGenetics, part of Exact Sciences	RCV003930184	SCV004743897	likely benign	SYNE1-related condition	2019-04-05	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).