Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28845 | 86758;86759;86760 | chr2:178559599;178559598;178559597 | chr2:179424326;179424325;179424324 |
| N2AB | 27204 | 81835;81836;81837 | chr2:178559599;178559598;178559597 | chr2:179424326;179424325;179424324 |
| N2A | 26277 | 79054;79055;79056 | chr2:178559599;178559598;178559597 | chr2:179424326;179424325;179424324 |
| N2B | 19780 | 59563;59564;59565 | chr2:178559599;178559598;178559597 | chr2:179424326;179424325;179424324 |
| Novex-1 | 19905 | 59938;59939;59940 | chr2:178559599;178559598;178559597 | chr2:179424326;179424325;179424324 |
| Novex-2 | 19972 | 60139;60140;60141 | chr2:178559599;178559598;178559597 | chr2:179424326;179424325;179424324 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.001 | N | 0.26 | 0.044 | 0.0482279557977 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/I | rs1488272613  |
-0.507 | 0.086 | N | 0.477 | 0.334 | 0.272205846399 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1488272613 |
-0.507 | 0.086 | N | 0.477 | 0.334 | 0.272205846399 | gnomAD-4.0.0 | 6.84211E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99478E-07 | 0 | 0 |
| T/N | None | None | 0.01 | N | 0.299 | 0.346 | 0.226586394389 | gnomAD-4.0.0 | 6.84211E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15942E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1224 | likely_benign | 0.1208 | benign | -0.822 | Destabilizing | 0.001 | N | 0.26 | neutral | N | 0.458341915 | None | None | I |
| T/C | 0.313 | likely_benign | 0.3467 | ambiguous | -0.462 | Destabilizing | 0.714 | D | 0.368 | neutral | None | None | None | None | I |
| T/D | 0.7789 | likely_pathogenic | 0.7769 | pathogenic | 0.041 | Stabilizing | 0.013 | N | 0.395 | neutral | None | None | None | None | I |
| T/E | 0.718 | likely_pathogenic | 0.714 | pathogenic | -0.016 | Destabilizing | 0.043 | N | 0.401 | neutral | None | None | None | None | I |
| T/F | 0.5072 | ambiguous | 0.525 | ambiguous | -1.227 | Destabilizing | 0.703 | D | 0.498 | neutral | None | None | None | None | I |
| T/G | 0.3532 | ambiguous | 0.3074 | benign | -0.977 | Destabilizing | 0.044 | N | 0.349 | neutral | None | None | None | None | I |
| T/H | 0.4917 | ambiguous | 0.4939 | ambiguous | -1.335 | Destabilizing | 0.47 | N | 0.39 | neutral | None | None | None | None | I |
| T/I | 0.3491 | ambiguous | 0.3999 | ambiguous | -0.518 | Destabilizing | 0.086 | N | 0.477 | neutral | N | 0.488915538 | None | None | I |
| T/K | 0.5724 | likely_pathogenic | 0.5737 | pathogenic | -0.494 | Destabilizing | 0.059 | N | 0.39 | neutral | None | None | None | None | I |
| T/L | 0.2262 | likely_benign | 0.2385 | benign | -0.518 | Destabilizing | 0.111 | N | 0.411 | neutral | None | None | None | None | I |
| T/M | 0.1662 | likely_benign | 0.1759 | benign | -0.077 | Destabilizing | 0.73 | D | 0.382 | neutral | None | None | None | None | I |
| T/N | 0.2688 | likely_benign | 0.2698 | benign | -0.289 | Destabilizing | 0.01 | N | 0.299 | neutral | N | 0.462008763 | None | None | I |
| T/P | 0.3327 | likely_benign | 0.3072 | benign | -0.592 | Destabilizing | 0.02 | N | 0.491 | neutral | N | 0.454202745 | None | None | I |
| T/Q | 0.5019 | ambiguous | 0.506 | ambiguous | -0.606 | Destabilizing | 0.17 | N | 0.458 | neutral | None | None | None | None | I |
| T/R | 0.5268 | ambiguous | 0.525 | ambiguous | -0.209 | Destabilizing | 0.539 | D | 0.462 | neutral | None | None | None | None | I |
| T/S | 0.0764 | likely_benign | 0.077 | benign | -0.601 | Destabilizing | None | N | 0.071 | neutral | N | 0.443201891 | None | None | I |
| T/V | 0.2321 | likely_benign | 0.2686 | benign | -0.592 | Destabilizing | 0.082 | N | 0.323 | neutral | None | None | None | None | I |
| T/W | 0.8333 | likely_pathogenic | 0.8369 | pathogenic | -1.1 | Destabilizing | 0.965 | D | 0.499 | neutral | None | None | None | None | I |
| T/Y | 0.487 | ambiguous | 0.4886 | ambiguous | -0.865 | Destabilizing | 0.703 | D | 0.465 | 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.