Description
This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 37 of the MC4R protein (p.Asp37Val). This variant is present in population databases (rs13447325, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features associated with MC4R-related obesity (PMID: 12970296). ClinVar contains an entry for this variant (Variation ID: 14319). 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 MC4R protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect MC4R function (PMID: 16752916). 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 |
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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 |