Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Elsea Laboratory, |
RCV001250091 | SCV001424226 | uncertain significance | Beta-hydroxyisobutyryl-CoA deacylase deficiency | 2020-04-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001250091 | SCV003472437 | likely pathogenic | Beta-hydroxyisobutyryl-CoA deacylase deficiency | 2023-06-13 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HIBCH protein function. ClinVar contains an entry for this variant (Variation ID: 973469). This missense change has been observed in individual(s) with 3-hydroxyisobutryl-CoA hydrolase deficiency (PMID: 32677093; external communication). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs758938066, gnomAD 0.009%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 118 of the HIBCH protein (p.Phe118Ser). |