ClinVar Miner

Submissions for variant NM_000060.2(BTD):c.933delT (p.Ser311Argfs) (rs397514395)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000021974 SCV000220396 likely pathogenic Biotinidase deficiency 2014-06-09 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078082 SCV000230007 pathogenic not provided 2016-06-20 criteria provided, single submitter clinical testing
GeneDx RCV000078082 SCV000238755 pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing The c.933delT variant has been previously reported in association with profound biotinidasedeficiency (Pomponio et al., 1997; Norrgard et al., 1999). The c.933delT variant is not observed inlarge population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome VariantServer). The deletion causes a frameshift starting with codon Serine 311, changes this amino acid to anArginine residue and creates a premature Stop codon at position 23 of the new reading frame, denotedp.Ser311ArgfsX23. This variant is predicted to cause loss of normal protein function through proteintruncation. In summary, we interpret c.933delT to be pathogenic.
Invitae RCV000021974 SCV000630340 pathogenic Biotinidase deficiency 2018-06-01 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BTD gene (p.Ser311Argfs*23). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 233 amino acids of the BTD protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with other BTD variants in individuals affected with profound biotinidase deficiency (PMID: 9396567, 12359137, 22698809, 10400129, 27657684) and partial biotinidase deficiency (PMID: 25174816, 17185019). ClinVar contains an entry for this variant (Variation ID: 25052). This variant has been observed in individuals with BTD enzyme activity <10% of the mean normal activity, findings that are highly specific for biotinidase deficiency (PMID: 10400129, 17185019, 9396567). For these reasons, this variant has been classified as Pathogenic.
Research and Development, ARUP Laboratories RCV000021974 SCV000042644 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only

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