Submissions for variant NM_001370658.1(BTD):c.820A>G (p.Ile274Val)

gnomAD frequency: 0.01187  dbSNP: rs35976361

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224487	SCV000280765	likely benign	not provided	2015-09-28	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Illumina Laboratory Services, Illumina	RCV000021969	SCV000441826	likely benign	Biotinidase deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Counsyl	RCV000021969	SCV000800817	likely benign	Biotinidase deficiency	2018-06-06	criteria provided, single submitter	clinical testing
Mendelics	RCV000021969	SCV001136345	likely benign	Biotinidase deficiency	2019-05-28	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000021969	SCV001652842	likely benign	Biotinidase deficiency	2021-05-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000021969	SCV001729954	benign	Biotinidase deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265566	SCV002548199	benign	not specified	2022-05-17	criteria provided, single submitter	clinical testing	Variant summary: BTD c.820A>G (p.Ile274Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0032 in 251404 control chromosomes, predominantly at a frequency of 0.042 within the African or African-American subpopulation in the gnomAD database, including 15 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 9.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in BTD causing Biotinidase Deficiency phenotype (0.0046), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000224487	SCV002774132	likely benign	not provided	2021-07-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000224487	SCV002821166	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	BTD: BP4, BS1, BS2
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000021969	SCV004810123	benign	Biotinidase deficiency	2024-04-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000224487	SCV005264660	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000021969	SCV001454450	benign	Biotinidase deficiency	2019-10-30	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003964809	SCV004783040	likely benign	BTD-related disorder	2023-02-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).