Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17943 | 54052;54053;54054 | chr2:178605468;178605467;178605466 | chr2:179470195;179470194;179470193 |
| N2AB | 16302 | 49129;49130;49131 | chr2:178605468;178605467;178605466 | chr2:179470195;179470194;179470193 |
| N2A | 15375 | 46348;46349;46350 | chr2:178605468;178605467;178605466 | chr2:179470195;179470194;179470193 |
| N2B | 8878 | 26857;26858;26859 | chr2:178605468;178605467;178605466 | chr2:179470195;179470194;179470193 |
| Novex-1 | 9003 | 27232;27233;27234 | chr2:178605468;178605467;178605466 | chr2:179470195;179470194;179470193 |
| Novex-2 | 9070 | 27433;27434;27435 | chr2:178605468;178605467;178605466 | chr2:179470195;179470194;179470193 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/S | None | None | 0.062 | N | 0.525 | 0.139 | 0.648878273322 | gnomAD-4.0.0 | 6.85078E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00364E-07 | 0 | 0 |
| I/T | rs769817623  |
-0.426 | None | N | 0.307 | 0.105 | 0.486494567076 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| I/T | rs769817623 |
-0.426 | None | N | 0.307 | 0.105 | 0.486494567076 | gnomAD-4.0.0 | 7.53586E-06 | None | None | None | None | I | None | 0 | 2.23884E-05 | None | 0 | 0 | None | 0 | 0 | 8.10328E-06 | 1.16214E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2108 | likely_benign | 0.2158 | benign | -0.507 | Destabilizing | 0.035 | N | 0.361 | neutral | None | None | None | None | I |
| I/C | 0.5875 | likely_pathogenic | 0.5686 | pathogenic | -0.61 | Destabilizing | 0.824 | D | 0.442 | neutral | None | None | None | None | I |
| I/D | 0.8098 | likely_pathogenic | 0.7626 | pathogenic | -0.056 | Destabilizing | 0.38 | N | 0.573 | neutral | None | None | None | None | I |
| I/E | 0.6628 | likely_pathogenic | 0.6286 | pathogenic | -0.158 | Destabilizing | 0.38 | N | 0.571 | neutral | None | None | None | None | I |
| I/F | 0.1727 | likely_benign | 0.1494 | benign | -0.608 | Destabilizing | 0.001 | N | 0.269 | neutral | N | 0.470015638 | None | None | I |
| I/G | 0.6279 | likely_pathogenic | 0.6146 | pathogenic | -0.645 | Destabilizing | 0.38 | N | 0.555 | neutral | None | None | None | None | I |
| I/H | 0.5761 | likely_pathogenic | 0.5367 | ambiguous | 0.05 | Stabilizing | 0.935 | D | 0.561 | neutral | None | None | None | None | I |
| I/K | 0.4764 | ambiguous | 0.4489 | ambiguous | -0.198 | Destabilizing | 0.38 | N | 0.573 | neutral | None | None | None | None | I |
| I/L | 0.1585 | likely_benign | 0.1489 | benign | -0.275 | Destabilizing | 0.012 | N | 0.303 | neutral | N | 0.468418128 | None | None | I |
| I/M | 0.1108 | likely_benign | 0.1041 | benign | -0.336 | Destabilizing | 0.317 | N | 0.403 | neutral | N | 0.509976749 | None | None | I |
| I/N | 0.411 | ambiguous | 0.3622 | ambiguous | -0.005 | Destabilizing | 0.317 | N | 0.576 | neutral | N | 0.519806953 | None | None | I |
| I/P | 0.868 | likely_pathogenic | 0.8408 | pathogenic | -0.32 | Destabilizing | 0.555 | D | 0.575 | neutral | None | None | None | None | I |
| I/Q | 0.5117 | ambiguous | 0.4861 | ambiguous | -0.24 | Destabilizing | 0.555 | D | 0.574 | neutral | None | None | None | None | I |
| I/R | 0.3517 | ambiguous | 0.3192 | benign | 0.343 | Stabilizing | 0.38 | N | 0.573 | neutral | None | None | None | None | I |
| I/S | 0.3534 | ambiguous | 0.3276 | benign | -0.46 | Destabilizing | 0.062 | N | 0.525 | neutral | N | 0.485310378 | None | None | I |
| I/T | 0.1632 | likely_benign | 0.1597 | benign | -0.453 | Destabilizing | None | N | 0.307 | neutral | N | 0.512515622 | None | None | I |
| I/V | 0.079 | likely_benign | 0.0803 | benign | -0.32 | Destabilizing | None | N | 0.177 | neutral | N | 0.407329597 | None | None | I |
| I/W | 0.7366 | likely_pathogenic | 0.6752 | pathogenic | -0.609 | Destabilizing | 0.935 | D | 0.589 | neutral | None | None | None | None | I |
| I/Y | 0.5042 | ambiguous | 0.4632 | ambiguous | -0.347 | Destabilizing | 0.235 | N | 0.453 | 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.