ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.674G>A (p.Cys225Tyr)

gnomAD frequency: 0.00001  dbSNP: rs397507175
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724643 SCV000230003 likely pathogenic not provided 2015-03-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000021959 SCV000817625 pathogenic Biotinidase deficiency 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 245 of the BTD protein (p.Cys245Tyr). This variant is present in population databases (rs397507175, gnomAD 0.002%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 15776412, 28971021). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 38281). 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. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000021959 SCV002017996 pathogenic Biotinidase deficiency 2019-08-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000021959 SCV002506313 likely pathogenic Biotinidase deficiency 2022-02-22 criteria provided, single submitter clinical testing The BTD c.734G>A; p.Cys245Tyr variant (rs397507175) is reported in the literature in multiple individuals affected with profound biotinidase deficiency usually (Jay 2015, Porta 2017, Wolf 2005). This variant is reported in ClinVar (Variation ID: 38281) and is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The cysteine at codon 245 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.924). Based on available information, this variant is considered to be likely pathogenic. References: Jay AM et al. Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years. Genet Med. 2015 Mar;17(3):205-9. PMID: 25144890. Porta F et al. Neonatal screening for biotinidase deficiency: A 30-year single center experience. Mol Genet Metab Rep. 2017 Sep 20;13:80-82. PMID: 28971021. Wolf B et al. Biotinidase deficiency: novel mutations and their biochemical and clinical correlates. Hum Mutat. 2005 Apr;25(4):413. PMID: 15776412.
Baylor Genetics RCV000021959 SCV004211407 pathogenic Biotinidase deficiency 2023-10-12 criteria provided, single submitter clinical testing
Counsyl RCV000021959 SCV000797130 likely pathogenic Biotinidase deficiency 2019-03-02 no assertion criteria provided clinical testing

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