Submissions for variant NM_001370658.1(BTD):c.68A>G (p.His23Arg)

gnomAD frequency: 0.00042  dbSNP: rs146011150

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000022030	SCV000943282	uncertain significance	Biotinidase deficiency	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 43 of the BTD protein (p.His43Arg). This variant is present in population databases (rs146011150, gnomAD 0.07%). This missense change has been observed in individual(s) with a positive newborn screening result for BTD-related disease (PMID: 26810761). ClinVar contains an entry for this variant (Variation ID: 38483). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000022030	SCV001440042	likely benign	Biotinidase deficiency	2019-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002513289	SCV003698460	uncertain significance	Inborn genetic diseases	2022-06-29	criteria provided, single submitter	clinical testing	The c.128A>G (p.H43R) alteration is located in exon 2 (coding exon 2) of the BTD gene. This alteration results from a A to G substitution at nucleotide position 128, causing the histidine (H) at amino acid position 43 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics	RCV000022030	SCV003835547	uncertain significance	Biotinidase deficiency	2022-10-22	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000022030	SCV000607107	not provided	Biotinidase deficiency		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001251701	SCV001427442	uncertain significance	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000022030	SCV001454447	uncertain significance	Biotinidase deficiency	2020-02-04	no assertion criteria provided	clinical testing