Protein Structure Prediction, human variation (Week 5)

.0001 MARFAN SYNDROME, SEVERE CLASSIC

FBN1, ARG1137PRO [dbSNP:rs137854456] ClinVar

According to OMIM, a G to C transversion at nucleotide 3410 converted codon 1137 from CGC (arginine) to CCC (Proline) is associated with this gene. This mutation was previously known as ARG239PRO. This is a nonconservative change where a basic amnio acid is replaced with a nonpolar alpha-amino acid proline. There appeared to be no clinical impact of this mutation as the two original patients this was identified in did not show any abnormalities. 

Protein Analysis:

The substitution of Arginine with Proline on Codon 1137 did not have any significant impact on the secondary structure, hydropathy, or transmembrane region of the protein. The alpha and  beta regions of the secondary structure are hydrophilic and the same was noted on the variant mutation. Upon magnification of the Kyte Doolittle regions, all areas remained hydrophobic in both sequences. There was no change on the transmembrane regions of the protein. 

Original Sequence: Overall view of secondary structure

Original sequence: Magnified view of secondary structure

Variant Sequence: Overall view of secondary structure

Variant sequence: Magnified view of secondary structure

Orignial sequence: Overall view of Kyte Doolittle Regions

Originial sequence: Magnified view of Kyte Doolittle Region

Variant sequence: Overall view of Kyte Doolittle Region

Variant Sequence: Magnified view of Kyte Doolittle Region

Originial sequence: Overall view of transmembrane regions

Originial sequence: Magnified view of transmembrane regions

Variant sequence: Overall view of transmembrane regions

Variant sequence: Magnified view of transmembrane regions

Originial Sequence Helical Wheel

Variant Sequence Helical Wheel