Submissions for variant NM_001370658.1(BTD):c.1144A>G (p.Asn382Asp)

gnomAD frequency: 0.00001  dbSNP: rs147188293

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001959733	SCV002210323	uncertain significance	Biotinidase deficiency	2021-09-24	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine with aspartic acid at codon 402 of the BTD protein (p.Asn402Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs147188293, ExAC 0.02%). This variant has not been reported in the literature in individuals with BTD-related conditions. 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 aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.