Submissions for variant NM_001370658.1(BTD):c.682A>C (p.Ile228Leu)

dbSNP: rs398123140

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001301669	SCV001490846	likely pathogenic	Biotinidase deficiency	2022-11-29	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 248 of the BTD protein (p.Ile248Leu). This missense change has been observed in individual(s) with biotinidase deficiency (Invitae). This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 1004892). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Ile248 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22698809, 26810761). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.