Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002038794 | SCV002310305 | uncertain significance | Biotinidase deficiency | 2021-07-31 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BTD-related conditions. This variant is present in population databases (rs559136372, ExAC 0.01%). This sequence change replaces histidine with proline at codon 450 of the BTD protein (p.His450Pro). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and proline. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999617 | SCV005625379 | uncertain significance | not provided | 2024-09-10 | criteria provided, single submitter | clinical testing | The BTD c.1349A>C (p.His450Pro) variant has not been reported in individuals with BTD-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251434 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |