ClinVar Miner

Submissions for variant NM_014384.2(ACAD8):c.1129G>A (p.Gly377Ser) (rs121908419)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000081615 SCV000330899 pathogenic not provided 2016-08-18 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000005687 SCV000369043 likely pathogenic Deficiency of isobutyryl-CoA dehydrogenase 2017-04-27 criteria provided, single submitter clinical testing The ACAD8 c.1129G>A (p.Gly377Ser) missense variant has been reported in two studies in which it was identified in four individuals diagnosed with isobutyryl-CoA dehydrogenase (IBD) deficiency through newborn screening, including in one in a homozygous state, in two in a compound heterozygous state, and in a heterozygous state in one individual with a mild phenotype (Oglesbee et al. 2007; Scolamiero et al. 2015). Oglesbee et al. (2007) used cultured fibroblasts from the IBD-deficient newborns to confirm biochemically the diagnosis of ICD deficiency. Control data are unavailable for this variant, which is reported at a frequency of 0.00012 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Gly377Ser variant is classified as likely pathogenic for isobutyryl-CoA dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx RCV000081615 SCV000490391 pathogenic not provided 2015-06-09 criteria provided, single submitter clinical testing The G377S missense change in the ACAD8 gene has been reported previously in association with isobutyryl-CoA dehydrogenase (IBD) deficiency as G355S, using numbering based on the processed protein (Oglesbee et al., 2007). It occurs in a very well-conserved position of the IBD protein and in silico analysis predicts this change to be damaging to the IBD protein. Therefore, we interpret G377S as a pathogenic variant.
OMIM RCV000005687 SCV000025869 pathogenic Deficiency of isobutyryl-CoA dehydrogenase 2007-02-01 no assertion criteria provided literature only
GenomeConnect, ClinGen RCV000005687 SCV000607346 not provided Deficiency of isobutyryl-CoA dehydrogenase no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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