Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004783550 | SCV005394183 | likely pathogenic | Biotinidase deficiency | 2024-09-27 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.1280A>G (p.His427Arg), also reported as H447R, results in a non-conservative amino acid change located in the Vanin, C-terminal domain (IPR043957) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251440 control chromosomes. c.1280A>G has been reported in the literature in the presumed compound heterozygous state in at least 1 individual affected with partial Biotinidase Deficiency (example, Seker Yilmaz_2018). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal activity in patient cells in the presence of the common pathogenic variant p.Asp444His (example, Tanyalcin_2016, Seker Yilmaz_2018). A different variant affecting the same codon has been reported as pathogenic in ClinVar (c.1279C>T, p.His427Tyr), supporting the critical relevance of codon 427 to BTD protein function. The following publications have been ascertained in the context of this evaluation (PMID: 29353266, 27760515). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic. |