ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.218A>G (p.Tyr73Cys)

dbSNP: rs397514348
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000021911 SCV000798916 likely pathogenic Biotinidase deficiency 2018-03-28 criteria provided, single submitter clinical testing
Invitae RCV000021911 SCV001590142 pathogenic Biotinidase deficiency 2024-01-05 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 93 of the BTD protein (p.Tyr93Cys). This variant is present in population databases (rs397514348, gnomAD 0.003%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 12359137, 25144890, 26810761; Invitae). ClinVar contains an entry for this variant (Variation ID: 24993). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTD protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000021911 SCV004099989 pathogenic Biotinidase deficiency 2023-09-19 criteria provided, single submitter clinical testing Variant summary: BTD c.218A>G (p.Tyr73Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five 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 251380 control chromosomes (gnomAD). c.218A>G (also known as c.278A>G/p.Y93C) has been reported in the literature in multiple individuals affected with Biotinidase Deficiency (examples: Wolf_2002, Jay_2016, Procter_2016, Maguolo_2021, Akgun_2021). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 34448386, 25144890, 34136440, 26810761, 12359137). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000021911 SCV004211418 pathogenic Biotinidase deficiency 2023-10-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000021911 SCV002081547 pathogenic Biotinidase deficiency 2021-06-10 no assertion criteria provided clinical testing

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