ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.1421A>G (p.Tyr474Cys)

dbSNP: rs750598655
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670347 SCV000795188 uncertain significance Biotinidase deficiency 2017-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000670347 SCV002292282 uncertain significance Biotinidase deficiency 2022-08-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 494 of the BTD protein (p.Tyr494Cys). This variant is present in population databases (rs750598655, gnomAD 0.0009%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 26810761, 28498829; Invitae). ClinVar contains an entry for this variant (Variation ID: 554671). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004702295 SCV005205373 uncertain significance not specified 2024-06-03 criteria provided, single submitter clinical testing Variant summary: BTD c.1421A>G (p.Tyr474Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251422 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1421A>G has been reported in the literature in the heterozygous and compound heterozygous states in individuals affected with Biotinidase Deficiency (e.g. Procter_2016, Borsatto_2017, Carvalho_2020, Yilmaz_2024). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28498829, 31801038, 26810761, 38141137). ClinVar contains an entry for this variant (Variation ID: 554671). Based on the evidence outlined above, the variant was classified as uncertain significance.

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