Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33322 | 100189;100190;100191 | chr2:178537145;178537144;178537143 | chr2:179401872;179401871;179401870 |
| N2AB | 31681 | 95266;95267;95268 | chr2:178537145;178537144;178537143 | chr2:179401872;179401871;179401870 |
| N2A | 30754 | 92485;92486;92487 | chr2:178537145;178537144;178537143 | chr2:179401872;179401871;179401870 |
| N2B | 24257 | 72994;72995;72996 | chr2:178537145;178537144;178537143 | chr2:179401872;179401871;179401870 |
| Novex-1 | 24382 | 73369;73370;73371 | chr2:178537145;178537144;178537143 | chr2:179401872;179401871;179401870 |
| Novex-2 | 24449 | 73570;73571;73572 | chr2:178537145;178537144;178537143 | chr2:179401872;179401871;179401870 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | rs775769503  |
0.308 | 0.958 | N | 0.495 | 0.271 | 0.351830644314 | gnomAD-2.1.1 | 5.64E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.619E-04 | None | 0 | 5.34E-05 | 0 |
| W/C | rs775769503 |
0.308 | 0.958 | N | 0.495 | 0.271 | 0.351830644314 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| W/C | rs775769503 |
0.308 | 0.958 | N | 0.495 | 0.271 | 0.351830644314 | gnomAD-4.0.0 | 6.57194E-06 | None | None | None | None | I | None | 2.41301E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| W/G | rs760971514 |
-0.917 | 0.302 | N | 0.419 | 0.265 | 0.32082282376 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| W/G | rs760971514 |
-0.917 | 0.302 | N | 0.419 | 0.265 | 0.32082282376 | gnomAD-4.0.0 | 1.36863E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31959E-05 | 0 |
| W/R | None | None | 0.68 | N | 0.608 | 0.236 | 0.364926071151 | gnomAD-4.0.0 | 6.84313E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1598E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.3425 | ambiguous | 0.3197 | benign | -0.493 | Destabilizing | 0.003 | N | 0.159 | neutral | None | None | None | None | I |
| W/C | 0.6154 | likely_pathogenic | 0.5964 | pathogenic | 0.117 | Stabilizing | 0.958 | D | 0.495 | neutral | N | 0.400288981 | None | None | I |
| W/D | 0.7204 | likely_pathogenic | 0.672 | pathogenic | 1.002 | Stabilizing | 0.738 | D | 0.604 | neutral | None | None | None | None | I |
| W/E | 0.7061 | likely_pathogenic | 0.6693 | pathogenic | 1.02 | Stabilizing | 0.538 | D | 0.501 | neutral | None | None | None | None | I |
| W/F | 0.1978 | likely_benign | 0.1914 | benign | -0.228 | Destabilizing | 0.582 | D | 0.389 | neutral | None | None | None | None | I |
| W/G | 0.3565 | ambiguous | 0.3043 | benign | -0.606 | Destabilizing | 0.302 | N | 0.419 | neutral | N | 0.356228773 | None | None | I |
| W/H | 0.586 | likely_pathogenic | 0.5541 | ambiguous | 0.235 | Stabilizing | 0.968 | D | 0.492 | neutral | None | None | None | None | I |
| W/I | 0.4466 | ambiguous | 0.4165 | ambiguous | -0.186 | Destabilizing | 0.223 | N | 0.43 | neutral | None | None | None | None | I |
| W/K | 0.7116 | likely_pathogenic | 0.6275 | pathogenic | 0.261 | Stabilizing | 0.365 | N | 0.482 | neutral | None | None | None | None | I |
| W/L | 0.2629 | likely_benign | 0.2337 | benign | -0.186 | Destabilizing | None | N | 0.151 | neutral | N | 0.343915623 | None | None | I |
| W/M | 0.3361 | likely_benign | 0.3306 | benign | -0.154 | Destabilizing | 0.008 | N | 0.146 | neutral | None | None | None | None | I |
| W/N | 0.6375 | likely_pathogenic | 0.6029 | pathogenic | -0.023 | Destabilizing | 0.896 | D | 0.578 | neutral | None | None | None | None | I |
| W/P | 0.5546 | ambiguous | 0.5461 | ambiguous | -0.28 | Destabilizing | 0.002 | N | 0.164 | neutral | None | None | None | None | I |
| W/Q | 0.6287 | likely_pathogenic | 0.6033 | pathogenic | 0.146 | Stabilizing | 0.738 | D | 0.579 | neutral | None | None | None | None | I |
| W/R | 0.6434 | likely_pathogenic | 0.5481 | ambiguous | 0.233 | Stabilizing | 0.68 | D | 0.608 | neutral | N | 0.349052084 | None | None | I |
| W/S | 0.3389 | likely_benign | 0.3158 | benign | -0.405 | Destabilizing | 0.178 | N | 0.439 | neutral | N | 0.34414491 | None | None | I |
| W/T | 0.3895 | ambiguous | 0.373 | ambiguous | -0.341 | Destabilizing | 0.365 | N | 0.416 | neutral | None | None | None | None | I |
| W/V | 0.3302 | likely_benign | 0.2989 | benign | -0.28 | Destabilizing | 0.111 | N | 0.346 | neutral | None | None | None | None | I |
| W/Y | 0.3692 | ambiguous | 0.3495 | ambiguous | -0.431 | Destabilizing | 0.738 | D | 0.459 | 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.