ClinVar Miner

Submissions for variant NM_001609.4(ACADSB):c.68dup (p.Leu23fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004018294 SCV004847417 likely pathogenic Deficiency of 2-methylbutyryl-CoA dehydrogenase 2024-01-08 criteria provided, single submitter clinical testing The p.Leu23PhefsX25 variant in ACADSB has not been previously reported in individuals with short/branched chain acyl-CoA dehydrogenase deficiency (SBCAD, also known as 2-methylbutyryl-CoA dehydrogenase deficiency) but has been identified in 0.002% (1/41438) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 23 and leads to a premature termination codon 25 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function of the ACADSB gene is an established disease mechanism in autosomal recessive SBCAD. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive short/branched chain acyl-CoA dehydrogenase deficiency (SBCAD). ACMG/AMP Criteria applied: PVS1, PM2_Supporting.

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