ClinVar Miner

Submissions for variant NM_000183.3(HADHB):c.255-1G>A

gnomAD frequency: 0.00001  dbSNP: rs112842641
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001261548 SCV003785524 pathogenic Mitochondrial trifunctional protein deficiency 2024-01-02 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the HADHB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HADHB are known to be pathogenic (PMID: 9259266, 12754706). This variant is present in population databases (rs112842641, gnomAD 0.008%). Disruption of this splice site 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: 916614). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Department of Medical Genetics, University Hospital of North Norway RCV001261548 SCV001244851 uncertain significance Mitochondrial trifunctional protein deficiency 2020-04-24 no assertion criteria provided clinical testing

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