Submissions for variant NM_001378030.1(CCDC78):c.267G>A (p.Glu89=)

dbSNP: rs1246932109

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001058477	SCV001223051	uncertain significance	Congenital myopathy with internal nuclei and atypical cores	2020-02-21	criteria provided, single submitter	clinical testing	This sequence change affects codon 89 of the CCDC78 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CCDC78 protein. This variant also falls at the last nucleotide of exon 3 of the CCDC78 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CCDC78-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.