See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Liebig et al [2006], Merritt et al [2014], Evans et al [2016], Pena et al [2016], and Hesse et al [2018] report a total of 307 individuals with clinically diagnosed VLCAD, most ascertained by newborn screening. The number of observed vs expected sequence variants across the entire group is 97%. However, only Hesse et al [2018] performed systematic enzyme assays in their entire study population of 108 individuals. For the 55 individuals with enzyme activity that was 0%-24% of control, all pathogenic variants were identified through sequence analysis. For the smaller group, which was designated as an overlap affected/carrier group (n=7) with enzyme activity 25%-27% of control, only 57% had two variants identified through sequence analysis. In this table, the 95% reflects only the data reported by Hesse et al [2018], calculated across both subgroups. Note: The Hesse et al [2018] article does not state that all individuals in the overlap group are affected; that is, some individuals may have only one pathogenic variant, not biallelic pathogenic variants.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Pervaiz et al [2011], Miller et al [2015]