ClinVar Miner

Submissions for variant NM_001918.5(DBT):c.1333_1336del (p.Met444_Asn445insTer)

dbSNP: rs2100761028
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001911936 SCV002145565 pathogenic Maple syrup urine disease 2021-04-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn445*) in the DBT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the DBT protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with maple syrup urine disease (PMID: 23313820). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the DBT protein. Other variant(s) that disrupt this region (p.Ser461*) have been determined to be pathogenic (PMID: 30228974). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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