Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230890 | SCV003928836 | likely pathogenic | Mitochondrial trifunctional protein deficiency | 2023-04-19 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exons 2-3 in the HADHB gene. A presumed nomenclature of c.(-9+1_-8-1)_(109+1_110-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a large deletion that removes the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream site. An alternative downstream in-frame start codon (p.Met75) is located in exon 5 of the encoded protein. However, start loss variant c.1A>G is classified pathogenic in ClinVar (ID 418241). The variant was absent in 21694 control chromosomes (gnomAD structural variants data set). c.(-9+1_-8-1)_(109+1_110-1)del has been reported in the literature in an individual affected with Mitochondrial Trifunctional Protein Deficiency and authors reported that this occurrence was de novo (example: Boutron_2011). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 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. |