Submissions for variant NM_001985.3(ETFB):c.341_375+154del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002868020	SCV003235985	likely pathogenic	Multiple acyl-CoA dehydrogenase deficiency	2022-10-07	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with ETFB-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 3 (c.341_375+154del) of the ETFB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ETFB are known to be pathogenic (PMID: 16510302, 23785301). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts a region of the ETFB protein in which other variant(s) (p.Glu115del) have been observed in individuals with ETFB-related conditions (PMID: 30626930). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.