Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000493651 | SCV000583375 | pathogenic | not provided | 2022-07-15 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Functional studies demonstrate markedly reduced 3-Hydroxy-isobutyry-CoA hydrolase activity in a patient with HIBCH deficiency.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31395954, 3202239, 32022391) |
| Laboratory for Molecular Medicine, |
RCV001195536 | SCV001365914 | likely pathogenic | Beta-hydroxyisobutyryl-CoA deacylase deficiency | 2019-08-09 | criteria provided, single submitter | clinical testing | The p.Leu284PhefsX10 variant in HIBCH has not been reported in any other families with HIBCH deficiency and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 284 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function variants in the HIBCH gene have been reported in several individuals with HIBCH deficiency. 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 HIBCH deficiency. ACMG/AMP Criteria applied: PVS1, PM2. |
| OMIM | RCV001195536 | SCV004697946 | pathogenic | Beta-hydroxyisobutyryl-CoA deacylase deficiency | 2024-02-29 | no assertion criteria provided | literature only |