ClinVar Miner

Submissions for variant NM_000017.4(ACADS):c.529T>C (p.Trp177Arg) (rs57443665)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004032 SCV000220594 likely pathogenic Deficiency of butyryl-CoA dehydrogenase 2014-08-22 criteria provided, single submitter literature only
GeneDx RCV000185684 SCV000238605 pathogenic not provided 2018-09-14 criteria provided, single submitter clinical testing The W177R missense variant in the ACADS gene has been reported previously in association with short chainacyl-CoA dehydrogenase (SCAD) deficiency using alternative nomenclature (Gregersen et al., 1998). Functionalanalysis of the W177R variant found that it is associated with significantly reduced enzyme activity compared towild-type (Gregersen et al., 1998). The W177R variant is a non-conservative amino acid substitution, which is likelyto impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Thissubstitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probablydamaging to the protein structure/function. In summary, we interpret W177R as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000004032 SCV000611158 pathogenic Deficiency of butyryl-CoA dehydrogenase 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000004032 SCV000632509 pathogenic Deficiency of butyryl-CoA dehydrogenase 2020-01-05 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 177 of the ACADS protein (p.Trp177Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is present in population databases (rs57443665, ExAC 0.6%). This variant has been reported as homozygous or compound heterozygous in multiple individuals with SCAD deficiency (PMID: 9499414, 22241096, 18676165, 12736383). ClinVar contains an entry for this variant (Variation ID: 3828). Experimental studies have shown this variant causes aggregation and abolishes enzymatic activity of the encoded protein (PMID: 9499414, 18523805). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000185684 SCV000703978 pathogenic not provided 2017-01-06 criteria provided, single submitter clinical testing
OMIM RCV000004032 SCV000024198 pathogenic Deficiency of butyryl-CoA dehydrogenase 1998-04-01 no assertion criteria provided literature only
Reproductive Health Research and Development,BGI Genomics RCV000004032 SCV001142438 pathogenic Deficiency of butyryl-CoA dehydrogenase 2020-01-06 no assertion criteria provided curation NM_000017.2:c.529T>C in the ACADS gene has an allele frequency of 0.007 in Africa subpopulation in the gnomAD database. Functional studies demonstrate that c.529T>C has affected aggregation and abolishes enzymatic activity of the encoded protein (PMID: 9499414; 18523805). It was detected in multiple individuals with autosomal recessive Deficiency of butyryl-CoA dehydrogenase, two homozygous c.529T>C (p.Trp177Arg), compound heterozygous with c.988C>T (p.Arg330Cys) (PMID: 22241096; 18676165; 12736383). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP criteria applied: PS3; PM3_Strong; PP4.

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