Table 2.
PolyPhen and TreeSAAP results for each missense polymorphisms used in the study. Each rare variant is defined by which part of the triglyceride phenotype distribution it was found (H = high, M = Middle, L= Low) according to Romeo et al. [3]. For the five common missense variants, Significant and NonSig (Nonsignificant) refers to phenotypic associations from the Treescan analyses. The Biological Assay column refers to assays in Table 3 of Romeo et al. [4]. A “-“ means no tests were performed. All significant PolyPhen predictions are in bold. All TreeSAAP properties considered significant with a score of 6 or more [13] are reported, all with an extreme value of 8 are in bold. The TreeSAAP property symbol key is provided below.
| Missense Variant | Phenotype Distribution | Biological Assay | PolyPhen Score | PolyPhen Prediction | TreeSAAP Property |
|---|---|---|---|---|---|
| M-1-T | M | - | NA | benign | |
| P-5-L | M | - | NA | benign | αc, αn, K0, Hp |
| E-40-K | Significant | - | 1.424 | benign | pHi |
| M-41-I | NonSig | - | 1.16 | benign | |
| S-67-R | M | - | 1.563 | possibly damaging | |
| R-72-L | M | - | 1.958 | possibly damaging | H, Hnc, αn |
| E-167-K | L | LPL Inhib | 0.194 | benign | pHi |
| P-174-S | M | - | 1.715 | possibly damaging | |
| E-190-Q | NonSig | - | 0.243 | benign | |
| E-196-K | M | - | 1.541 | possibly damaging | pHi, El |
| G-223-R | L | Secretion | 2.065 | probably damaging | E’sm |
| R-230-C | M | - | 2.792 | probably damaging | pHi, E’sm, Et, Br, Ns, C |
| F-237-V | M | - | 2.51 | probably damaging | |
| P-251-T | H | Nothing | 1.781 | possibly damaging | |
| T-266-M | NonSig | - | 0.783 | benign | K0, Ht |
| R-278-Q | Significant | - | 0.644 | benign | pHi |
| V-291-M | M | - | 1.012 | benign | |
| L-293-M | M | - | 1.236 | benign | |
| E-296-V | M | - | 2.057 | probably damaging | Ns, Pβ, Br, H, Ra |
| P-307-S | M | - | 0.955 | benign | αc |
| V-308-M | M | - | 1.199 | benign | |
| R-336-C | L | Secretion | 2.255 | probably damaging | Br, pHi, Et, Ns, C, Ca, Hnc |
| D-338-E | M | - | 1.626 | possibly damaging | |
| W-349-C | L | Secretion | 3.677 | probably damaging | |
| Ca, E’sm, Mv, Mw, Hnc, V0, | |||||
| G-361-R | L | Secretion | 2.274 | probably damaging | μ |
| R-371-Q | H | Nothing | 1.558 | possibly damaging | pHi |
| R-384-W | L | Secretion | 2.304 | probably damaging | Br, Ht |
| TreeSAAP Property Key | |||
|---|---|---|---|
| Alpha-helical tendency | Pα | Molecular weight | Mw |
| Average # of surrounding residues | Ns | Normalized hydrophobicity | Hnc |
| Beta-structure tendency | Pβ | Partial specific volume | V0 |
| Buriedness | Br | Power to be at the C-terminal | αc |
| Composition | C | Power to be at the N-terminal | αn |
| Compressibility | K0 | Refractive index | μ |
| Helical contact | Ca | Short-range & medium-range nonbonded energy | E’sm |
| Hydropathy | H | Solvent accessible reduction ratio | Ra |
| Isoelectric point | pHi | Surrounding hydrophobicity | Hp |
| Long-range nonbonded energy | El | Thermodyn. transfer hydrophobicity | Ht |
| Molecular volume | Mv | Total non-bonded energy | Et |