Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671749 | SCV000796765 | uncertain significance | Biotinidase deficiency | 2017-12-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000671749 | SCV000933704 | pathogenic | Biotinidase deficiency | 2024-01-29 | criteria provided, single submitter | clinical testing | This variant occurs in a non-coding region of the BTD gene. It does not change the encoded amino acid sequence of the BTD protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with biotinidase deficiency (PMID: 11313766). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as 12236G>A. ClinVar contains an entry for this variant (Variation ID: 555845). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298730 | SCV002598709 | uncertain significance | not specified | 2022-09-04 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.*159G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 6e-05 in 150958 control chromosomes (gnomAD v3.1.2). c.*159G>A, also known in the literature as 12236G>A, has been reported as a biallelic genotype in three siblings affected with severe Biotinidase Deficiency. Unaffected heterozygous family members carrying the variant of interest reportedly had 60% normal biotinidase activity (Muhl_2001). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance and one as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Prevention |
RCV003945702 | SCV004763273 | uncertain significance | BTD-related disorder | 2024-02-12 | no assertion criteria provided | clinical testing | The BTD c.*159G>A variant is located in the 3' untranslated region. This variant was reported in compound heterozygous state with BTD pathogenic variant in three siblings from single family, one sibling was affected with biotinidase deficiency, two other children were clinically asymptomatic at the time of testing. All three siblings had 3.4-4.6 % of residual enzymatic activity as compared to normal values, heterozygote carriers within the family had about 60% residual enzymatic activity (reported as 12236G>A, Table 2, Muhl et al. 2001. PubMed ID: 11313766). This variant has not been reported in a large population database, indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |