Submissions for variant NM_001985.3(ETFB):c.124T>C (p.Cys42Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003476359	SCV004194759	pathogenic	Multiple acyl-CoA dehydrogenase deficiency	2023-02-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003476359	SCV004223223	pathogenic	Multiple acyl-CoA dehydrogenase deficiency	2023-11-28	criteria provided, single submitter	clinical testing	Variant summary: ETFB c.124T>C (p.Cys42Arg) results in a non-conservative amino acid change located in the electron transfer flavoprotein, alpha/beta-subunit, N-terminal domain (IPR014730) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251388 control chromosomes (gnomAD). c.124T>C has been reported in the literature as a biallelic genotype in individuals affected with Glutaric Aciduria, Type 2b (e.g. Curcoy_2003, Schiff_2006, Distelmaier_2007). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Henriques_2010). The variant resulted in impaired ETF folding and assembly and showed no detectable enzyme activity. The following publications have been ascertained in the context of this evaluation (PMID: 12706375, 17638024, 20674745, 16510302). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.