Description
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 not expected to disrupt HDAC8 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. This variant disrupts the p.Met196 amino acid residue in HDAC8. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25102094, 25805374). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with HDAC8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 196 of the HDAC8 protein (p.Met196Thr).
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |