Submissions for variant NM_001370658.1(BTD):c.175C>T (p.Arg59Cys)

gnomAD frequency: 0.00001  dbSNP: rs104893687

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000001982	SCV000487041	pathogenic	Biotinidase deficiency	2016-09-28	criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV000001982	SCV001430585	likely pathogenic	Biotinidase deficiency	2019-06-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001815158	SCV002062442	likely pathogenic	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000001982	SCV002236290	pathogenic	Biotinidase deficiency	2024-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 79 of the BTD protein (p.Arg79Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 10801053, 27845546). ClinVar contains an entry for this variant (Variation ID: 1905). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BTD protein function with a positive predictive value of 95%. This variant disrupts the p.Arg79 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14707518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000001982	SCV002803666	pathogenic	Biotinidase deficiency	2024-04-05	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000001982	SCV004211437	pathogenic	Biotinidase deficiency	2024-03-22	criteria provided, single submitter	clinical testing
OMIM	RCV000001982	SCV000022140	pathogenic	Biotinidase deficiency	2000-03-01	no assertion criteria provided	literature only
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence,	RCV000001982	SCV002073679	likely pathogenic	Biotinidase deficiency		no assertion criteria provided	clinical testing