ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.873del (p.Ser291fs) (rs397514395)

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Total submissions: 7
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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 2020-02-06 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation, as the last 233 amino acids are replaced with 22 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27657684, 10400129, 20549359, 9396567)
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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000021974 SCV001473123 pathogenic Biotinidase deficiency 2020-05-27 criteria provided, single submitter clinical testing The BTD c.933delT; p.Ser311fs variant (rs397514395) is reported in the literature in the compound heterozygous state in multiple individuals affected with profound or partial biotinidase deficiency (Borsatto 2014, Milankovics 2007, Pomponio 1997, Wolf 2002, Wolf 2017). This variant is found on only three chromosomes in the Genome Aggregation Database (3/282788 alleles), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide in the last exon of the BTD gene. While this is not expected to lead to nonsense-mediated decay, this is predicted to result in a truncated protein lacking the last 233 amino acids of the BTD protein. Based on available information, this variant is considered to be pathogenic. References: Borsatto T et al. Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients. BMC Med Genet. 2014;15:96. Milankovics I et al. Mutations causing biotinidase deficiency in children ascertained by newborn screening in Western Hungary. Mol Genet Metab. 2007;90(3):345-348. Pomponio RJ et al. Mutations in the human biotinidase gene that cause profound biotinidase deficiency in symptomatic children: molecular, biochemical, and clinical analysis. Pediatr Res. 1997;42(6):840-848. Wolf B et al. Seventeen novel mutations that cause profound biotinidase deficiency. Mol Genet Metab. 2002;77(1-2):108-111. Wolf B. Successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening. Genet Med. 2017;19(4):396-402.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000078082 SCV001500291 pathogenic not provided 2021-03-01 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV000021974 SCV000042644 pathogenic Biotinidase deficiency 2017-02-17 no assertion criteria provided literature only

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