Submissions for variant NM_001370658.1(BTD):c.1254T>A (p.Tyr418Ter)

dbSNP: rs397514416

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000022005	SCV000220888	likely pathogenic	Biotinidase deficiency	2014-11-14	criteria provided, single submitter	literature only
GeneDx	RCV002281043	SCV002569662	pathogenic	not provided	2022-03-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 106 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 30912303, 15060693)
Baylor Genetics	RCV000022005	SCV004211484	pathogenic	Biotinidase deficiency	2022-09-07	criteria provided, single submitter	clinical testing
Invitae	RCV000022005	SCV004293425	pathogenic	Biotinidase deficiency	2023-02-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr438*) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 106 amino acid(s) of the BTD protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with biotinidase deficiency (PMID: 15060693, 30912303). ClinVar contains an entry for this variant (Variation ID: 25080). This variant disrupts a region of the BTD protein in which other variant(s) (p.His485Gln) have been determined to be pathogenic (PMID: 25967232, 26810761, 30912303; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.