ClinVar Miner

Submissions for variant NM_000183.3(HADHB):c.998C>T (p.Pro333Leu)

gnomAD frequency: 0.00001  dbSNP: rs770736746
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001261547 SCV004526687 likely pathogenic Mitochondrial trifunctional protein deficiency 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 333 of the HADHB protein (p.Pro333Leu). This variant is present in population databases (rs770736746, gnomAD 0.006%). This missense change has been observed in individual(s) with mitochondrial trifunctional protein deficiency (PMID: 35433169). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 916538). 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 HADHB protein function with a positive predictive value of 80%. 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.
Department of Medical Genetics, University Hospital of North Norway RCV001261547 SCV001244852 uncertain significance Mitochondrial trifunctional protein deficiency 2018-08-15 no assertion criteria provided clinical testing

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