Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002664295 | SCV003525122 | pathogenic | Biotinidase deficiency | 2022-06-25 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 439 of the BTD protein (p.Ala439Asp). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 26203071, 28649532). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002664295 | SCV005185819 | pathogenic | Biotinidase deficiency | 2024-05-30 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.1256C>A (p.Ala419Asp; also known as p.Ala439Asp in the literature) results in a non-conservative amino acid change in 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 251418 control chromosomes (gnomAD). c.1256C>A has been reported in the literature in individuals affected with both partial and profound biotinidase deficiency (Funghini_2020, Senanayake_2015, Bottin_2015), including two homozygous individuals where it was found in cis with another benign variant c.1353T>C (p.Cys451Cys; Senanayake_2015, Bottin_2015). All individuals who carried the variant showed reduced enzymatic activity, with homozygous individuals exhibiting <10% of normal activity. These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 26203071, 33312878, 28649532). ClinVar contains an entry for this variant (Variation ID: 2203320). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV002664295 | SCV005660295 | pathogenic | Biotinidase deficiency | 2024-06-11 | criteria provided, single submitter | clinical testing |