Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000001981 | SCV001748683 | pathogenic | Biotinidase deficiency | 2021-06-29 | criteria provided, single submitter | clinical testing | Variant summary: BTD c.[1147T>G;1270G>C] (p.[Phe383Val;Asp424His]) variant, also known as c.[1207T>G;1330G>C] (p.[Phe403Val;Asp444His]), is a complex allele and involves the alteration of multiple nucleotides. The allele frequency of this complex variant could not be determined from large population databases such as gnomAD because the individual variants of the complex have variable frequencies and the exact number of alleles representing a combination of the two in cis is unknown. However, based on the frequency of the least prevalent allele, namely c.1147T>G, it can be estimated that the complex variant allele will be found at a frequency not to exceed 1.6e-05 in 251384 control chromosomes. This variant frequency is not higher than expected for a pathogenic variant in BTD causing Biotinidase Deficiency phenotype (0.0046). c.[1147T>G;1270G>C] has been reported in the literature in individuals affected with Biotinidase Deficiency (e.g. Norrgard_1999, Hesermann_2012, Al Hosani_2014, Haines_2014, Jay_2015). Importantly, patients homozygous for this complex variant were all reported with profound Biotinidase Deficiency and markedly reduced or absent enzyme activity (e.g. Norrgard_1999, Hesermann_2012, Haines_2014). These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000001981 | SCV000022139 | pathogenic | Biotinidase deficiency | 1999-07-01 | no assertion criteria provided | literature only |