Submissions for variant NM_001370658.1(BTD):c.1569C>A (p.Asp523Glu)

gnomAD frequency: 0.00024  dbSNP: rs146136265

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078071	SCV000109909	pathogenic	not provided	2018-01-03	criteria provided, single submitter	clinical testing
Invitae	RCV000022028	SCV000630332	pathogenic	Biotinidase deficiency	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 543 of the BTD protein (p.Asp543Glu). This variant is present in population databases (rs146136265, gnomAD 0.06%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 25174816, 25967232, 28498829). ClinVar contains an entry for this variant (Variation ID: 25103). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000078071	SCV000888013	pathogenic	not provided	2018-08-24	criteria provided, single submitter	clinical testing
Mendelics	RCV000022028	SCV001136351	pathogenic	Biotinidase deficiency	2019-05-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000022028	SCV003835260	pathogenic	Biotinidase deficiency	2022-08-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000078071	SCV004039642	likely pathogenic	not provided	2023-09-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as D543E; This variant is associated with the following publications: (PMID: 25967232, 26810761, 25174816, 22698809, 28498829, 35167647, 31801038)
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000022028	SCV004183396	likely pathogenic	Biotinidase deficiency	2020-03-03	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4, PM2, PM3, PP2
Counsyl	RCV000022028	SCV000798766	likely pathogenic	Biotinidase deficiency	2018-03-30	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000022028	SCV001461231	pathogenic	Biotinidase deficiency	2020-09-16	no assertion criteria provided	clinical testing