Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22301 | 67126;67127;67128 | chr2:178580478;178580477;178580476 | chr2:179445205;179445204;179445203 |
| N2AB | 20660 | 62203;62204;62205 | chr2:178580478;178580477;178580476 | chr2:179445205;179445204;179445203 |
| N2A | 19733 | 59422;59423;59424 | chr2:178580478;178580477;178580476 | chr2:179445205;179445204;179445203 |
| N2B | 13236 | 39931;39932;39933 | chr2:178580478;178580477;178580476 | chr2:179445205;179445204;179445203 |
| Novex-1 | 13361 | 40306;40307;40308 | chr2:178580478;178580477;178580476 | chr2:179445205;179445204;179445203 |
| Novex-2 | 13428 | 40507;40508;40509 | chr2:178580478;178580477;178580476 | chr2:179445205;179445204;179445203 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs772823241  |
0.046 | 0.822 | N | 0.423 | 0.268 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 0 | 1.78E-05 | 0 |
| N/S | rs772823241 |
0.046 | 0.822 | N | 0.423 | 0.268 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| N/S | rs772823241 |
0.046 | 0.822 | N | 0.423 | 0.268 | None | gnomAD-4.0.0 | 3.03787E-05 | None | None | None | None | N | None | 1.33554E-05 | 0 | None | 0 | 2.23724E-05 | None | 0 | 0 | 3.90016E-05 | 0 | 1.60251E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.257 | likely_benign | 0.2293 | benign | -0.127 | Destabilizing | 0.86 | D | 0.485 | neutral | None | None | None | None | N |
| N/C | 0.2849 | likely_benign | 0.2635 | benign | 0.292 | Stabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | N |
| N/D | 0.1625 | likely_benign | 0.1703 | benign | 0.216 | Stabilizing | 0.014 | N | 0.297 | neutral | N | 0.428929525 | None | None | N |
| N/E | 0.4559 | ambiguous | 0.4544 | ambiguous | 0.17 | Stabilizing | 0.754 | D | 0.402 | neutral | None | None | None | None | N |
| N/F | 0.6224 | likely_pathogenic | 0.6014 | pathogenic | -0.633 | Destabilizing | 0.978 | D | 0.683 | prob.neutral | None | None | None | None | N |
| N/G | 0.4128 | ambiguous | 0.3811 | ambiguous | -0.263 | Destabilizing | 0.86 | D | 0.401 | neutral | None | None | None | None | N |
| N/H | 0.1453 | likely_benign | 0.1344 | benign | -0.294 | Destabilizing | 0.99 | D | 0.536 | neutral | D | 0.534000907 | None | None | N |
| N/I | 0.2348 | likely_benign | 0.2105 | benign | 0.133 | Stabilizing | 0.89 | D | 0.589 | neutral | N | 0.484516236 | None | None | N |
| N/K | 0.4103 | ambiguous | 0.3908 | ambiguous | 0.158 | Stabilizing | 0.822 | D | 0.439 | neutral | N | 0.499154827 | None | None | N |
| N/L | 0.2715 | likely_benign | 0.2532 | benign | 0.133 | Stabilizing | 0.754 | D | 0.552 | neutral | None | None | None | None | N |
| N/M | 0.3873 | ambiguous | 0.3523 | ambiguous | 0.245 | Stabilizing | 0.994 | D | 0.649 | neutral | None | None | None | None | N |
| N/P | 0.3192 | likely_benign | 0.2992 | benign | 0.072 | Stabilizing | 0.978 | D | 0.628 | neutral | None | None | None | None | N |
| N/Q | 0.367 | ambiguous | 0.3433 | ambiguous | -0.209 | Destabilizing | 0.978 | D | 0.524 | neutral | None | None | None | None | N |
| N/R | 0.4367 | ambiguous | 0.4227 | ambiguous | 0.193 | Stabilizing | 0.978 | D | 0.526 | neutral | None | None | None | None | N |
| N/S | 0.1 | likely_benign | 0.0943 | benign | -0.009 | Destabilizing | 0.822 | D | 0.423 | neutral | N | 0.493018289 | None | None | N |
| N/T | 0.1591 | likely_benign | 0.1432 | benign | 0.075 | Stabilizing | 0.822 | D | 0.438 | neutral | N | 0.489940698 | None | None | N |
| N/V | 0.236 | likely_benign | 0.1994 | benign | 0.072 | Stabilizing | 0.16 | N | 0.411 | neutral | None | None | None | None | N |
| N/W | 0.842 | likely_pathogenic | 0.8363 | pathogenic | -0.723 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | None | None | None | None | N |
| N/Y | 0.2347 | likely_benign | 0.2419 | benign | -0.408 | Destabilizing | 0.99 | D | 0.641 | neutral | D | 0.534347623 | 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.