Submissions for variant NM_182961.4(SYNE1):c.23222A>G (p.Tyr7741Cys)

gnomAD frequency: 0.00014  dbSNP: rs34974663

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000339553	SCV000331483	uncertain significance	not provided	2017-07-03	criteria provided, single submitter	clinical testing
Invitae	RCV000647675	SCV000769473	uncertain significance	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2022-08-09	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 7670 of the SYNE1 protein (p.Tyr7670Cys). This variant is present in population databases (rs34974663, gnomAD 0.03%). 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: 281134). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.
Athena Diagnostics Inc	RCV000339553	SCV001475607	uncertain significance	not provided	2021-09-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519083	SCV003584966	uncertain significance	Inborn genetic diseases	2021-07-14	criteria provided, single submitter	clinical testing	The c.23009A>G (p.Y7670C) alteration is located in exon 127 (coding exon 126) of the SYNE1 gene. This alteration results from a A to G substitution at nucleotide position 23009, causing the tyrosine (Y) at amino acid position 7670 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000339553	SCV003824638	uncertain significance	not provided	2020-08-11	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000339553	SCV001807535	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000339553	SCV001920071	uncertain significance	not provided		no assertion criteria provided	clinical testing