Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657559 | SCV000779296 | likely pathogenic | not provided | 2018-05-18 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the SYNE1 gene. The c.19793dupA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.19793dupA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.19793dupA variant causes a frameshift starting with codon Alanine 6599, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 27 of the new reading frame, denoted p.Ala6599GlyfsX27. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Invitae | RCV002534257 | SCV003022426 | pathogenic | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2022-04-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545948). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Ala6599Glyfs*27) 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). |