ClinVar Miner

Submissions for variant NM_000183.3(HADHB):c.210-1G>T

gnomAD frequency: 0.00002  dbSNP: rs200777054
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483833 SCV000565053 likely pathogenic not provided 2017-02-02 criteria provided, single submitter clinical testing The c.210-1 G>T splice site variant in the HADHB gene has been previously reported in an infant with an abnormal newborn screen and cardiomyopathy where a deletion of exon 4 was also found; phase of the variants is unknown (Wang et al., 2012). This variant destroys the canonical splice acceptor site in intron 4, and is expected to cause abnormal gene splicing. In summary, c.210-1 G>T is interpreted to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001386845 SCV001587220 pathogenic Mitochondrial trifunctional protein deficiency 2024-01-29 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 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 (rs200777054, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with trifunctional protein deficiency (PMID: 22494545, 24314034). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 418243). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects HADHB function (PMID: 24314034). 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.
Baylor Genetics RCV004568144 SCV004191823 pathogenic Mitochondrial trifunctional protein deficiency 1 2024-03-18 criteria provided, single submitter clinical testing

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