ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.734C>T (p.Ser245Leu) (rs121434281)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000077894 SCV000232889 pathogenic not provided 2013-08-19 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000077894 SCV000511259 pathogenic not provided 2016-07-20 criteria provided, single submitter clinical testing
GeneDx RCV000077894 SCV000511934 likely pathogenic not provided 2016-11-15 criteria provided, single submitter clinical testing The S245L missense variant in the ACADM gene has been reported previously in a patient who was homozygous for the S245L variant and who was detected by newborn screening for medium chain acyl-CoA dehydrogenase (MCAD) deficiency. This patient had enzyme studies that showed residual MCAD activity between classical" MCAD deficiency and heterozygous carriers of MCAD deficiency (Zschocke et al., 2001). This variant has also been described in another patient who was compound heterozygous for S245L and another variant; this individual was reported to have significantly higher residual MCAD enzyme activity (Touw et al., 2013). The S245L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded."
Counsyl RCV000003781 SCV000792652 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-07-05 criteria provided, single submitter clinical testing
Invitae RCV000003781 SCV001199349 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-11-05 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 245 of the ACADM protein (p.Ser245Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs121434281, ExAC 0.004%). This variant has been reported in the literature in several individuals with biochemical profiles diagnostic for MCAD deficiency (PMID: 11409868, 23509891, 20434380, 22683754). ClinVar contains an entry for this variant (Variation ID: 3598). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000003781 SCV000023946 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2001-05-01 no assertion criteria provided literature only

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