Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000118480 | SCV000152886 | likely benign | not specified | 2013-08-26 | criteria provided, single submitter | clinical testing | |
EGL Genetic Diagnostics, |
RCV000726269 | SCV000343320 | uncertain significance | not provided | 2016-06-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000536058 | SCV000649168 | uncertain significance | Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2017-03-29 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 29 of the SYNE1 gene. It does not directly change the encoded amino acid sequence of the SYNE1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs376511242, ExAC 0.06%) but has not been reported in the literature in individuals with a SYNE1-related disease. ClinVar contains an entry for this variant (Variation ID: 130440). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. |