Submissions for variant NM_001985.3(ETFB):c.426_427insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTCTCCTGACCTCTAGATCCACCCGCCTCGGCCTCCCCAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGACAGCTGGATTTCTT (p.Asp143delinsPhePhePhePhePhePheXaaXaaXaaXaaSerProAspLeuTer)

dbSNP: rs2123580195

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001947884	SCV002195541	pathogenic	Multiple acyl-CoA dehydrogenase deficiency	2024-03-06	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the ETFB gene (c.426_427ins?), causing a frameshift at codon 143 (p.143fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ETFB-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ETFB are known to be pathogenic (PMID: 16510302, 23785301). For these reasons, this variant has been classified as Pathogenic.