ClinVar Miner

Submissions for variant NM_001918.4(DBT):c.670G>T (p.Glu224Ter) (rs74103423)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079951 SCV000231639 pathogenic not provided 2013-08-23 criteria provided, single submitter clinical testing
GeneDx RCV000079951 SCV000680731 pathogenic not provided 2018-10-25 criteria provided, single submitter clinical testing The E224X nonsense variant in the DBT gene has been previously reported in multiple patients with classic maple syrup urine disease (MSUD), both in the homozygous state and in the presence of a second pathogenic variant (Fisher et al., 1993). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This is supported by functional studies which demonstrate that cell lines with E224X variant result in a markedly truncated polypeptide compared with full-length wildtype (Fisher et al., 1993). In summary, we interpret E224X as pathogenic.
Invitae RCV000179397 SCV000834968 pathogenic Maple syrup urine disease 2020-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu224*) in the DBT gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs74103423, ExAC 0.1%). This variant has been reported in individuals affected with maple syrup urine disease (PMID: 8430702). ClinVar contains an entry for this variant (Variation ID: 94009). Loss-of-function variants in DBT are known to be pathogenic (PMID: 16579849, 16786533). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000179397 SCV000893167 pathogenic Maple syrup urine disease 2018-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000179397 SCV000485927 likely pathogenic Maple syrup urine disease 2016-11-03 no assertion criteria provided clinical testing

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