Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19229 | 57910;57911;57912 | chr2:178595669;178595668;178595667 | chr2:179460396;179460395;179460394 |
| N2AB | 17588 | 52987;52988;52989 | chr2:178595669;178595668;178595667 | chr2:179460396;179460395;179460394 |
| N2A | 16661 | 50206;50207;50208 | chr2:178595669;178595668;178595667 | chr2:179460396;179460395;179460394 |
| N2B | 10164 | 30715;30716;30717 | chr2:178595669;178595668;178595667 | chr2:179460396;179460395;179460394 |
| Novex-1 | 10289 | 31090;31091;31092 | chr2:178595669;178595668;178595667 | chr2:179460396;179460395;179460394 |
| Novex-2 | 10356 | 31291;31292;31293 | chr2:178595669;178595668;178595667 | chr2:179460396;179460395;179460394 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs778237029  |
0.11 | 0.003 | N | 0.27 | 0.057 | 0.0666544352282 | gnomAD-2.1.1 | 4.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.2E-06 | 0 |
| R/K | rs778237029 |
0.11 | 0.003 | N | 0.27 | 0.057 | 0.0666544352282 | gnomAD-4.0.0 | 5.49287E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30905E-06 | 0 | 1.66091E-05 |
| R/S | None | None | 0.338 | N | 0.493 | 0.104 | 0.149567049428 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4306 | ambiguous | 0.4868 | ambiguous | -0.045 | Destabilizing | 0.404 | N | 0.475 | neutral | None | None | None | None | N |
| R/C | 0.2653 | likely_benign | 0.3125 | benign | -0.342 | Destabilizing | 0.991 | D | 0.541 | neutral | None | None | None | None | N |
| R/D | 0.7909 | likely_pathogenic | 0.8151 | pathogenic | -0.404 | Destabilizing | 0.826 | D | 0.504 | neutral | None | None | None | None | N |
| R/E | 0.4587 | ambiguous | 0.5329 | ambiguous | -0.38 | Destabilizing | 0.404 | N | 0.492 | neutral | None | None | None | None | N |
| R/F | 0.5988 | likely_pathogenic | 0.6739 | pathogenic | -0.395 | Destabilizing | 0.826 | D | 0.525 | neutral | None | None | None | None | N |
| R/G | 0.3215 | likely_benign | 0.3726 | ambiguous | -0.147 | Destabilizing | 0.505 | D | 0.475 | neutral | N | 0.425469853 | None | None | N |
| R/H | 0.1524 | likely_benign | 0.166 | benign | -0.606 | Destabilizing | 0.906 | D | 0.531 | neutral | None | None | None | None | N |
| R/I | 0.3022 | likely_benign | 0.4107 | ambiguous | 0.178 | Stabilizing | 0.642 | D | 0.503 | neutral | N | 0.49671945 | None | None | N |
| R/K | 0.0752 | likely_benign | 0.0896 | benign | -0.294 | Destabilizing | 0.003 | N | 0.27 | neutral | N | 0.40858039 | None | None | N |
| R/L | 0.2259 | likely_benign | 0.2683 | benign | 0.178 | Stabilizing | 0.218 | N | 0.431 | neutral | None | None | None | None | N |
| R/M | 0.2028 | likely_benign | 0.2977 | benign | -0.197 | Destabilizing | 0.05 | N | 0.387 | neutral | None | None | None | None | N |
| R/N | 0.6362 | likely_pathogenic | 0.6862 | pathogenic | -0.209 | Destabilizing | 0.826 | D | 0.483 | neutral | None | None | None | None | N |
| R/P | 0.6388 | likely_pathogenic | 0.554 | ambiguous | 0.119 | Stabilizing | 0.906 | D | 0.516 | neutral | None | None | None | None | N |
| R/Q | 0.1175 | likely_benign | 0.1321 | benign | -0.234 | Destabilizing | 0.404 | N | 0.479 | neutral | None | None | None | None | N |
| R/S | 0.5906 | likely_pathogenic | 0.6361 | pathogenic | -0.339 | Destabilizing | 0.338 | N | 0.493 | neutral | N | 0.45375532 | None | None | N |
| R/T | 0.3034 | likely_benign | 0.393 | ambiguous | -0.231 | Destabilizing | 0.505 | D | 0.489 | neutral | N | 0.461028009 | None | None | N |
| R/V | 0.3676 | ambiguous | 0.4475 | ambiguous | 0.119 | Stabilizing | 0.404 | N | 0.505 | neutral | None | None | None | None | N |
| R/W | 0.2385 | likely_benign | 0.3219 | benign | -0.612 | Destabilizing | 0.991 | D | 0.555 | neutral | None | None | None | None | N |
| R/Y | 0.4888 | ambiguous | 0.5588 | ambiguous | -0.234 | Destabilizing | 0.967 | D | 0.517 | neutral | None | None | None | None | N |
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.