Submissions for variant NM_001370658.1(BTD):c.622G>T (p.Asp208Tyr)

dbSNP: rs397514380

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000185805	SCV000238747	pathogenic	not provided	2016-01-19	criteria provided, single submitter	clinical testing	The D228Y missense mutation in the BTD gene has been reported previously in association with biotinidase deficiency (Swango et al., 1998; ARUP BTD mutation database). Furthermore, another missense mutation at this position (D228G) and missense mutations in nearby residues (D222G, T234I) have been reported in association with biotinidase deficiency.
Eurofins Ntd Llc (ga)	RCV000185805	SCV000855891	uncertain significance	not provided	2017-08-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000185805	SCV002046648	likely pathogenic	not provided	2021-02-18	criteria provided, single submitter	clinical testing	The variant has been reported to be associated with partial biotinidase deficiency (PMID: 9654207 (1998)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is disease causing and damaging. Based on the available information, this variant is classified as likely pathogenic.
Baylor Genetics	RCV003473119	SCV004211405	likely pathogenic	Biotinidase deficiency	2023-10-14	criteria provided, single submitter	clinical testing
Invitae	RCV003473119	SCV004373059	pathogenic	Biotinidase deficiency	2023-09-08	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 228 of the BTD protein (p.Asp228Tyr). This variant is present in population databases (rs397514380, gnomAD 0.006%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 9654207; Invitae). 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: 25035). 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. This variant disrupts the p.Asp228 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 24797656; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.