ClinVar

Description

Variant summary: HADHA c.1981_1999del19 (p.Leu661SerfsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in patients (HGMD). This exonic variant is located close to a canonical splice-site and therefore could affect mRNA splicing: 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251460 control chromosomes. c.1981_1999del19 has been reported in the literature in a compound heterozygous individual affected with Mitochondrial trifunctional protein deficiency (Boutron_2011). This publication reported that the patient carried this variant had 39% of normal LCHAD activity measured from muscle tissue (Boutron_2011). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.