Associated disorders

The MMADHC gene is associated with autosomal recessive cobalamin D deficiency (MedGen UID: 341253)

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Pathogenic variants in the MMADHC gene are the only known cause of cobalamin D type methylmalonic acidemia.

The MMADHC gene encodes the cobalamin D enzyme, which is involved in the metabolism of cobalamin (vitamin B12) into its active forms, adenosylcobalamin and methylcobalamin. Adenosylcobalamin is a cofactor for the methylmalonyl-CoA mutase enzyme, which converts methylmalonyl-CoA to succinyl-CoA, a component of the Krebs cycle. Methylcobalamin is a cofactor for the methionine synthase enzyme, which converts homocysteine to methionine. Pathogenic variants in MMADHC can lead to decreased function of the methylmalonyl-CoA mutase enzyme, methionine synthase enzyme, or both enzymes, causing toxic accumulation of methylmalonic acid and/or homocysteine in the body.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
MMADHC NM_015702.2