Submissions for variant NM_182961.4(SYNE1):c.20263C>T (p.Arg6755Ter)

gnomAD frequency: 0.00001  dbSNP: rs780451185

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000993149	SCV001145919	pathogenic	not provided	2019-05-31	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000995657	SCV001149951	pathogenic	Autosomal recessive ataxia, Beauce type	2019-06-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001381375	SCV001579744	pathogenic	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2022-03-18	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with cerebellar ataxia (PMID: 25133958). This variant is present in population databases (rs780451185, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg6684*) in the SYNE1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNE1 are known to be pathogenic (PMID: 19542096, 24319099, 27086870). ClinVar contains an entry for this variant (Variation ID: 242515). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
CeGaT Center for Human Genetics Tuebingen	RCV000993149	SCV005434041	pathogenic	not provided	2024-10-01	criteria provided, single submitter	clinical testing	SYNE1: PVS1, PM2