Submissions for variant NM_182961.4(SYNE1):c.24139C>T (p.Arg8047Ter)

gnomAD frequency: 0.00001  dbSNP: rs1174316105

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000993164	SCV001145940	pathogenic	not provided	2019-02-18	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001390591	SCV001592375	pathogenic	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2022-06-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg7976*) 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). This variant is present in population databases (no rsID available, gnomAD 0.005%). 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: 632476). For these reasons, this variant has been classified as Pathogenic.