Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32384 | 97375;97376;97377 | chr2:178542704;178542703;178542702 | chr2:179407431;179407430;179407429 |
| N2AB | 30743 | 92452;92453;92454 | chr2:178542704;178542703;178542702 | chr2:179407431;179407430;179407429 |
| N2A | 29816 | 89671;89672;89673 | chr2:178542704;178542703;178542702 | chr2:179407431;179407430;179407429 |
| N2B | 23319 | 70180;70181;70182 | chr2:178542704;178542703;178542702 | chr2:179407431;179407430;179407429 |
| Novex-1 | 23444 | 70555;70556;70557 | chr2:178542704;178542703;178542702 | chr2:179407431;179407430;179407429 |
| Novex-2 | 23511 | 70756;70757;70758 | chr2:178542704;178542703;178542702 | chr2:179407431;179407430;179407429 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs754763137  |
0.016 | 0.334 | N | 0.373 | 0.099 | 0.495970961353 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs754763137 |
0.016 | 0.334 | N | 0.373 | 0.099 | 0.495970961353 | gnomAD-4.0.0 | 3.18266E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8585E-06 | 1.43295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0944 | likely_benign | 0.0948 | benign | -0.328 | Destabilizing | 0.001 | N | 0.157 | neutral | N | 0.383311878 | None | None | I |
| V/C | 0.5615 | ambiguous | 0.5475 | ambiguous | -0.792 | Destabilizing | 0.977 | D | 0.371 | neutral | None | None | None | None | I |
| V/D | 0.2242 | likely_benign | 0.2166 | benign | -0.292 | Destabilizing | 0.81 | D | 0.395 | neutral | N | 0.444611053 | None | None | I |
| V/E | 0.255 | likely_benign | 0.2435 | benign | -0.412 | Destabilizing | 0.617 | D | 0.381 | neutral | None | None | None | None | I |
| V/F | 0.1821 | likely_benign | 0.1643 | benign | -0.713 | Destabilizing | 0.896 | D | 0.367 | neutral | N | 0.480667854 | None | None | I |
| V/G | 0.1206 | likely_benign | 0.119 | benign | -0.386 | Destabilizing | 0.379 | N | 0.382 | neutral | N | 0.444611053 | None | None | I |
| V/H | 0.3999 | ambiguous | 0.3682 | ambiguous | -0.01 | Destabilizing | 0.992 | D | 0.405 | neutral | None | None | None | None | I |
| V/I | 0.0754 | likely_benign | 0.0743 | benign | -0.32 | Destabilizing | 0.334 | N | 0.373 | neutral | N | 0.447555358 | None | None | I |
| V/K | 0.3052 | likely_benign | 0.2595 | benign | -0.343 | Destabilizing | 0.617 | D | 0.379 | neutral | None | None | None | None | I |
| V/L | 0.1505 | likely_benign | 0.1453 | benign | -0.32 | Destabilizing | 0.201 | N | 0.393 | neutral | N | 0.450171589 | None | None | I |
| V/M | 0.1239 | likely_benign | 0.1156 | benign | -0.509 | Destabilizing | 0.972 | D | 0.334 | neutral | None | None | None | None | I |
| V/N | 0.1291 | likely_benign | 0.1296 | benign | -0.161 | Destabilizing | 0.85 | D | 0.409 | neutral | None | None | None | None | I |
| V/P | 0.2707 | likely_benign | 0.2544 | benign | -0.294 | Destabilizing | 0.92 | D | 0.405 | neutral | None | None | None | None | I |
| V/Q | 0.2481 | likely_benign | 0.2256 | benign | -0.375 | Destabilizing | 0.92 | D | 0.421 | neutral | None | None | None | None | I |
| V/R | 0.2935 | likely_benign | 0.2454 | benign | 0.105 | Stabilizing | 0.85 | D | 0.409 | neutral | None | None | None | None | I |
| V/S | 0.101 | likely_benign | 0.1029 | benign | -0.476 | Destabilizing | 0.447 | N | 0.364 | neutral | None | None | None | None | I |
| V/T | 0.1095 | likely_benign | 0.1028 | benign | -0.502 | Destabilizing | 0.021 | N | 0.297 | neutral | None | None | None | None | I |
| V/W | 0.7741 | likely_pathogenic | 0.718 | pathogenic | -0.769 | Destabilizing | 0.992 | D | 0.507 | neutral | None | None | None | None | I |
| V/Y | 0.4544 | ambiguous | 0.4166 | ambiguous | -0.488 | Destabilizing | 0.972 | D | 0.361 | 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.