Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000428786 | SCV000515923 | likely pathogenic | not provided | 2023-08-27 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.(A289V) using alternate nomenclature; This variant is associated with the following publications: (PMID: 26810761, 27657684, 10400129, 22698809, Sharma2021[Poster]) |
Counsyl | RCV000675056 | SCV000800511 | uncertain significance | Biotinidase deficiency | 2017-03-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000675056 | SCV002261716 | likely pathogenic | Biotinidase deficiency | 2021-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, a(n) neutral and non-polar amino acid, with valine, a(n) neutral and non-polar amino acid, at codon 289 of the BTD protein (p.Ala289Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 22698809). ClinVar contains an entry for this variant (Variation ID: 379232). 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"). This variant disrupts the p.Ala289 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10400129, 26810761, 27657684; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Natera, |
RCV000675056 | SCV002081564 | likely pathogenic | Biotinidase deficiency | 2021-10-01 | no assertion criteria provided | clinical testing |