Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26896 | 80911;80912;80913 | chr2:178565446;178565445;178565444 | chr2:179430173;179430172;179430171 |
| N2AB | 25255 | 75988;75989;75990 | chr2:178565446;178565445;178565444 | chr2:179430173;179430172;179430171 |
| N2A | 24328 | 73207;73208;73209 | chr2:178565446;178565445;178565444 | chr2:179430173;179430172;179430171 |
| N2B | 17831 | 53716;53717;53718 | chr2:178565446;178565445;178565444 | chr2:179430173;179430172;179430171 |
| Novex-1 | 17956 | 54091;54092;54093 | chr2:178565446;178565445;178565444 | chr2:179430173;179430172;179430171 |
| Novex-2 | 18023 | 54292;54293;54294 | chr2:178565446;178565445;178565444 | chr2:179430173;179430172;179430171 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.008 | N | 0.249 | 0.103 | 0.104622674875 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/V | rs1705407272  |
None | 0.901 | N | 0.605 | 0.321 | 0.349204839081 | gnomAD-4.0.0 | 7.96135E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.42975E-05 | 0 | 0 |
| D/Y | rs1327329522 |
-0.11 | 0.995 | N | 0.617 | 0.392 | 0.44750879378 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| D/Y | rs1327329522 |
-0.11 | 0.995 | N | 0.617 | 0.392 | 0.44750879378 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/Y | rs1327329522 |
-0.11 | 0.995 | N | 0.617 | 0.392 | 0.44750879378 | gnomAD-4.0.0 | 2.56396E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78803E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2681 | likely_benign | 0.2724 | benign | -0.397 | Destabilizing | 0.565 | D | 0.447 | neutral | N | 0.503578346 | None | None | N |
| D/C | 0.7471 | likely_pathogenic | 0.7759 | pathogenic | -0.13 | Destabilizing | 0.996 | D | 0.665 | neutral | None | None | None | None | N |
| D/E | 0.2824 | likely_benign | 0.2601 | benign | -0.447 | Destabilizing | 0.008 | N | 0.249 | neutral | N | 0.496516301 | None | None | N |
| D/F | 0.7203 | likely_pathogenic | 0.7125 | pathogenic | -0.221 | Destabilizing | 0.987 | D | 0.617 | neutral | None | None | None | None | N |
| D/G | 0.2476 | likely_benign | 0.2653 | benign | -0.65 | Destabilizing | 0.008 | N | 0.301 | neutral | N | 0.479418683 | None | None | N |
| D/H | 0.4185 | ambiguous | 0.4591 | ambiguous | -0.275 | Destabilizing | 0.986 | D | 0.503 | neutral | N | 0.47096244 | None | None | N |
| D/I | 0.4885 | ambiguous | 0.4831 | ambiguous | 0.235 | Stabilizing | 0.961 | D | 0.625 | neutral | None | None | None | None | N |
| D/K | 0.6187 | likely_pathogenic | 0.6302 | pathogenic | -0.075 | Destabilizing | 0.633 | D | 0.435 | neutral | None | None | None | None | N |
| D/L | 0.5552 | ambiguous | 0.5295 | ambiguous | 0.235 | Stabilizing | 0.923 | D | 0.607 | neutral | None | None | None | None | N |
| D/M | 0.6953 | likely_pathogenic | 0.7005 | pathogenic | 0.441 | Stabilizing | 0.996 | D | 0.633 | neutral | None | None | None | None | N |
| D/N | 0.1025 | likely_benign | 0.1186 | benign | -0.382 | Destabilizing | 0.075 | N | 0.231 | neutral | N | 0.452976168 | None | None | N |
| D/P | 0.5989 | likely_pathogenic | 0.6273 | pathogenic | 0.048 | Stabilizing | 0.961 | D | 0.483 | neutral | None | None | None | None | N |
| D/Q | 0.5489 | ambiguous | 0.5417 | ambiguous | -0.31 | Destabilizing | 0.858 | D | 0.447 | neutral | None | None | None | None | N |
| D/R | 0.6928 | likely_pathogenic | 0.694 | pathogenic | 0.122 | Stabilizing | 0.923 | D | 0.569 | neutral | None | None | None | None | N |
| D/S | 0.1709 | likely_benign | 0.1836 | benign | -0.528 | Destabilizing | 0.633 | D | 0.407 | neutral | None | None | None | None | N |
| D/T | 0.2783 | likely_benign | 0.3016 | benign | -0.334 | Destabilizing | 0.923 | D | 0.443 | neutral | None | None | None | None | N |
| D/V | 0.3331 | likely_benign | 0.3187 | benign | 0.048 | Stabilizing | 0.901 | D | 0.605 | neutral | N | 0.490283762 | None | None | N |
| D/W | 0.9419 | likely_pathogenic | 0.9482 | pathogenic | -0.077 | Destabilizing | 0.996 | D | 0.671 | neutral | None | None | None | None | N |
| D/Y | 0.291 | likely_benign | 0.3202 | benign | -0.001 | Destabilizing | 0.995 | D | 0.617 | neutral | N | 0.473431202 | 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.