Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3956 | 12091;12092;12093 | chr2:178741367;178741366;178741365 | chr2:179606094;179606093;179606092 |
| N2AB | 3639 | 11140;11141;11142 | chr2:178741367;178741366;178741365 | chr2:179606094;179606093;179606092 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3593 | 11002;11003;11004 | chr2:178741367;178741366;178741365 | chr2:179606094;179606093;179606092 |
| Novex-1 | 3718 | 11377;11378;11379 | chr2:178741367;178741366;178741365 | chr2:179606094;179606093;179606092 |
| Novex-2 | 3785 | 11578;11579;11580 | chr2:178741367;178741366;178741365 | chr2:179606094;179606093;179606092 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1156715113  |
None | 0.012 | N | 0.377 | 0.056 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1156715113 |
None | 0.012 | N | 0.377 | 0.056 | None | gnomAD-4.0.0 | 6.81622E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32336E-06 | 0 | 0 |
| I/V | rs2154318798 |
None | None | N | 0.195 | 0.041 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92976E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2154318798 |
None | None | N | 0.195 | 0.041 | None | gnomAD-4.0.0 | 6.56573E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.93424E-04 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3613 | ambiguous | 0.3671 | ambiguous | -1.473 | Destabilizing | None | N | 0.245 | neutral | None | None | None | None | I |
| I/C | 0.6473 | likely_pathogenic | 0.6691 | pathogenic | -0.867 | Destabilizing | 0.356 | N | 0.447 | neutral | None | None | None | None | I |
| I/D | 0.7144 | likely_pathogenic | 0.7254 | pathogenic | -0.829 | Destabilizing | 0.072 | N | 0.505 | neutral | None | None | None | None | I |
| I/E | 0.5997 | likely_pathogenic | 0.609 | pathogenic | -0.765 | Destabilizing | 0.031 | N | 0.431 | neutral | None | None | None | None | I |
| I/F | 0.2041 | likely_benign | 0.2151 | benign | -0.843 | Destabilizing | None | N | 0.235 | neutral | N | 0.45207474 | None | None | I |
| I/G | 0.6945 | likely_pathogenic | 0.7023 | pathogenic | -1.828 | Destabilizing | 0.016 | N | 0.399 | neutral | None | None | None | None | I |
| I/H | 0.5255 | ambiguous | 0.5495 | ambiguous | -0.89 | Destabilizing | 0.628 | D | 0.475 | neutral | None | None | None | None | I |
| I/K | 0.3948 | ambiguous | 0.4294 | ambiguous | -0.947 | Destabilizing | None | N | 0.443 | neutral | None | None | None | None | I |
| I/L | 0.1459 | likely_benign | 0.1474 | benign | -0.551 | Destabilizing | None | N | 0.206 | neutral | N | 0.4352853 | None | None | I |
| I/M | 0.1535 | likely_benign | 0.1584 | benign | -0.556 | Destabilizing | 0.171 | N | 0.422 | neutral | N | 0.45488587 | None | None | I |
| I/N | 0.3067 | likely_benign | 0.3275 | benign | -0.931 | Destabilizing | 0.055 | N | 0.501 | neutral | N | 0.45297197 | None | None | I |
| I/P | 0.8891 | likely_pathogenic | 0.9023 | pathogenic | -0.829 | Destabilizing | 0.136 | N | 0.516 | neutral | None | None | None | None | I |
| I/Q | 0.5114 | ambiguous | 0.5238 | ambiguous | -0.988 | Destabilizing | 0.072 | N | 0.543 | neutral | None | None | None | None | I |
| I/R | 0.2916 | likely_benign | 0.3179 | benign | -0.473 | Destabilizing | 0.038 | N | 0.496 | neutral | None | None | None | None | I |
| I/S | 0.313 | likely_benign | 0.3206 | benign | -1.563 | Destabilizing | 0.001 | N | 0.362 | neutral | N | 0.44517815 | None | None | I |
| I/T | 0.231 | likely_benign | 0.246 | benign | -1.369 | Destabilizing | 0.012 | N | 0.377 | neutral | N | 0.4255934 | None | None | I |
| I/V | 0.0665 | likely_benign | 0.0663 | benign | -0.829 | Destabilizing | None | N | 0.195 | neutral | N | 0.40371868 | None | None | I |
| I/W | 0.8335 | likely_pathogenic | 0.8524 | pathogenic | -0.956 | Destabilizing | 0.864 | D | 0.483 | neutral | None | None | None | None | I |
| I/Y | 0.5294 | ambiguous | 0.5569 | ambiguous | -0.701 | Destabilizing | 0.038 | N | 0.478 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.