Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27153 | 81682;81683;81684 | chr2:178564675;178564674;178564673 | chr2:179429402;179429401;179429400 |
| N2AB | 25512 | 76759;76760;76761 | chr2:178564675;178564674;178564673 | chr2:179429402;179429401;179429400 |
| N2A | 24585 | 73978;73979;73980 | chr2:178564675;178564674;178564673 | chr2:179429402;179429401;179429400 |
| N2B | 18088 | 54487;54488;54489 | chr2:178564675;178564674;178564673 | chr2:179429402;179429401;179429400 |
| Novex-1 | 18213 | 54862;54863;54864 | chr2:178564675;178564674;178564673 | chr2:179429402;179429401;179429400 |
| Novex-2 | 18280 | 55063;55064;55065 | chr2:178564675;178564674;178564673 | chr2:179429402;179429401;179429400 |
| 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 | rs908346441  |
-0.14 | 0.656 | N | 0.355 | 0.212 | 0.431822907236 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/I | rs908346441 |
-0.14 | 0.656 | N | 0.355 | 0.212 | 0.431822907236 | gnomAD-4.0.0 | 2.05305E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79908E-06 | 0 | 1.65728E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1639 | likely_benign | 0.1456 | benign | -0.489 | Destabilizing | 0.002 | N | 0.206 | neutral | N | 0.403809289 | None | None | I |
| V/C | 0.7597 | likely_pathogenic | 0.7468 | pathogenic | -0.773 | Destabilizing | 0.994 | D | 0.482 | neutral | None | None | None | None | I |
| V/D | 0.9633 | likely_pathogenic | 0.9553 | pathogenic | -0.441 | Destabilizing | 0.97 | D | 0.659 | neutral | N | 0.489384134 | None | None | I |
| V/E | 0.9211 | likely_pathogenic | 0.8895 | pathogenic | -0.557 | Destabilizing | 0.956 | D | 0.573 | neutral | None | None | None | None | I |
| V/F | 0.4496 | ambiguous | 0.4321 | ambiguous | -0.713 | Destabilizing | 0.97 | D | 0.489 | neutral | N | 0.472244612 | None | None | I |
| V/G | 0.554 | ambiguous | 0.5326 | ambiguous | -0.6 | Destabilizing | 0.698 | D | 0.534 | neutral | N | 0.478899975 | None | None | I |
| V/H | 0.9378 | likely_pathogenic | 0.9145 | pathogenic | -0.051 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | I |
| V/I | 0.131 | likely_benign | 0.1153 | benign | -0.345 | Destabilizing | 0.656 | D | 0.355 | neutral | N | 0.492103064 | None | None | I |
| V/K | 0.9026 | likely_pathogenic | 0.877 | pathogenic | -0.487 | Destabilizing | 0.956 | D | 0.586 | neutral | None | None | None | None | I |
| V/L | 0.5819 | likely_pathogenic | 0.5641 | pathogenic | -0.345 | Destabilizing | 0.489 | N | 0.383 | neutral | N | 0.514441206 | None | None | I |
| V/M | 0.3973 | ambiguous | 0.3278 | benign | -0.486 | Destabilizing | 0.993 | D | 0.411 | neutral | None | None | None | None | I |
| V/N | 0.8454 | likely_pathogenic | 0.8107 | pathogenic | -0.298 | Destabilizing | 0.978 | D | 0.675 | neutral | None | None | None | None | I |
| V/P | 0.9552 | likely_pathogenic | 0.9477 | pathogenic | -0.36 | Destabilizing | 0.978 | D | 0.623 | neutral | None | None | None | None | I |
| V/Q | 0.8485 | likely_pathogenic | 0.8045 | pathogenic | -0.553 | Destabilizing | 0.978 | D | 0.658 | neutral | None | None | None | None | I |
| V/R | 0.7992 | likely_pathogenic | 0.7655 | pathogenic | 0.087 | Stabilizing | 0.978 | D | 0.673 | neutral | None | None | None | None | I |
| V/S | 0.4164 | ambiguous | 0.3658 | ambiguous | -0.635 | Destabilizing | 0.754 | D | 0.523 | neutral | None | None | None | None | I |
| V/T | 0.3491 | ambiguous | 0.3019 | benign | -0.652 | Destabilizing | 0.86 | D | 0.305 | neutral | None | None | None | None | I |
| V/W | 0.9724 | likely_pathogenic | 0.9652 | pathogenic | -0.762 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | I |
| V/Y | 0.9017 | likely_pathogenic | 0.8934 | pathogenic | -0.482 | Destabilizing | 0.993 | D | 0.478 | 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.