ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.385T>C (p.Phe129Leu)

gnomAD frequency: 0.00001  dbSNP: rs397514359
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000021926 SCV001544374 likely pathogenic Biotinidase deficiency 2021-09-15 criteria provided, single submitter clinical testing 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 25007). This variant has been observed in individual(s) with biotinidase deficiency (PMID: 10400129; Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 149 of the BTD protein (p.Phe149Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004700264 SCV005202258 uncertain significance not specified 2024-07-30 criteria provided, single submitter clinical testing Variant summary: BTD c.385T>C (p.Phe129Leu) 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 was absent in 251264 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.385T>C has been reported in the literature in an individual affected with Biotinidase Deficiency (Norrgard_1999). These report(s) do not provide unequivocal conclusions about association of the variant with Biotinidase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 10400129). ClinVar contains an entry for this variant (Variation ID: 25007). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV000021926 SCV002081551 uncertain significance Biotinidase deficiency 2020-10-26 no assertion criteria provided clinical testing

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