ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.751G>T (p.Ala251Ser)

gnomAD frequency: 0.00002  dbSNP: rs144575084
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001327642 SCV001518727 uncertain significance Biotinidase deficiency 2020-08-24 criteria provided, single submitter clinical testing This variant is present in population databases (rs144575084, ExAC 0.02%). This sequence change replaces alanine with serine at codon 271 of the BTD protein (p.Ala271Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant has not been reported in the literature in individuals with BTD-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15").
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800982 SCV002046497 likely pathogenic not provided 2020-12-10 criteria provided, single submitter clinical testing This variant has been reported only briefly in the published literature in a three-year-old girl where it was observed to have a residual biotinidase activity of 2-8% when compound heterozygous with another BTD variant (Woidy, Tsiakas, Murko, and Santer, https://doi.org/10.1007/s00112-020-00864-5). A related variant occurring in the same codon was found in a compound heterozygous boy affected with profound biotinidase deficiency (PMID: 22698809 (2012)). Based on the available information, the variant is predicted to be likely pathogenic.

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