ClinVar Miner

Submissions for variant NM_000017.4(ACADS):c.1138C>T (p.Arg380Trp) (rs28940875)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185699 SCV000238620 pathogenic not provided 2016-05-16 criteria provided, single submitter clinical testing The R380W missense pathogenic variant in the ACADS gene has been reported previously in association with short chain acyl-CoA dehydrogenase (SCAD) deficiency (Corydon et al. 2001; Edhager et al. 2014). Expression studies in E-coli found that R380W is associated with no detectable short chain acyl-CoA dehydrogenase compared to wild-type (Corydon et al. 2001). In summary, we interpret R380W to be a pathogenic variant.
Invitae RCV000004041 SCV000756744 pathogenic Deficiency of butyryl-CoA dehydrogenase 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 380 of the ACADS protein (p.Arg380Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs28940875, ExAC 0.04%). This variant has been reported to segregate with SCAD deficiency in a single family (PMID: 14595061) and has been reported in the homozygous state in several symptomatic individuals affected this condition (PMID: 24485985, 16926354). It has also been reported in the heterozygous state in several affected individuals in combination with the benign variant c.625G>A (p.Gly209Ser) (PMID: 11134486, 16906473, 22424739, 14595061). This variant is also known in the literature as Arg365Trp. ClinVar contains an entry for this variant (Variation ID: 3837). Experimental studies have shown that this missense, change disrupts ACADS protein ability to form tetramers and chaperone complexes (PMID: 18523805). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004041 SCV000024207 pathogenic Deficiency of butyryl-CoA dehydrogenase 2001-01-01 no assertion criteria provided literature only
Counsyl RCV000004041 SCV000220689 pathogenic Deficiency of butyryl-CoA dehydrogenase 2018-10-16 no assertion criteria provided clinical testing

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