Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778682 | SCV000915025 | uncertain significance | Biotinidase deficiency | 2018-10-29 | criteria provided, single submitter | clinical testing | The BTD c.101_104delGCTG (p.Gly34ValfsTer35) variant is a frameshift variant that is predicted to result in an absent or truncated protein. A literature search for the gene, cDNA change, and protein change did not reveal any clinical reports of this variant in individuals with biotinidase deficiency. In a retrospective analysis of carrier screening in 17638 chromosomes from ethnically diverse populations, Haque et al. (2016) identified the p.Gly34ValfsTer35 variant in one Caucasian allele. The variant is also reported at a frequency of 0.000363 in the European American population of the Exome Sequencing Project. Based on the potential impact of frameshift variants and the lack of clarifying evidence, the p.Gly34ValfsTer35 variant is classified as a variant of unknown significance but suspicious for pathogenicity for biotinidase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Ce |
RCV001090471 | SCV001246038 | pathogenic | not provided | 2018-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000778682 | SCV001587423 | pathogenic | Biotinidase deficiency | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly34Valfs*35) in the BTD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BTD are known to be pathogenic (PMID: 20083419). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with biotinidase deficiency (PMID: 7550325, 27657684, 27845546, 28220409; Invitae). ClinVar contains an entry for this variant (Variation ID: 631911). For these reasons, this variant has been classified as Pathogenic. |
Arcensus | RCV000778682 | SCV002564587 | likely pathogenic | Biotinidase deficiency | 2013-02-01 | criteria provided, single submitter | clinical testing |