Description
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 323 of the BTD protein (p.His323Arg). This variant is present in population databases (rs397507176, gnomAD 1.7%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individuals with partial BTD deficiency who showed 10-30% of normal BTD enzymatic activity (PMID: 9654207, 26361991). ClinVar contains an entry for this variant (Variation ID: 38278). 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. Experimental studies have shown that this missense change affects BTD function (PMID: 9654207, 24797656). 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.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
