Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33637 | 101134;101135;101136 | chr2:178535706;178535705;178535704 | chr2:179400433;179400432;179400431 |
| N2AB | 31996 | 96211;96212;96213 | chr2:178535706;178535705;178535704 | chr2:179400433;179400432;179400431 |
| N2A | 31069 | 93430;93431;93432 | chr2:178535706;178535705;178535704 | chr2:179400433;179400432;179400431 |
| N2B | 24572 | 73939;73940;73941 | chr2:178535706;178535705;178535704 | chr2:179400433;179400432;179400431 |
| Novex-1 | 24697 | 74314;74315;74316 | chr2:178535706;178535705;178535704 | chr2:179400433;179400432;179400431 |
| Novex-2 | 24764 | 74515;74516;74517 | chr2:178535706;178535705;178535704 | chr2:179400433;179400432;179400431 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.966 | N | 0.39 | 0.149 | 0.251639045875 | gnomAD-4.0.0 | 2.40065E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| D/N | None | None | 0.991 | N | 0.486 | 0.212 | 0.284150004643 | gnomAD-4.0.0 | 2.05269E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69843E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7871 | likely_pathogenic | 0.4603 | ambiguous | -0.207 | Destabilizing | 0.992 | D | 0.499 | neutral | N | 0.471200222 | None | None | I |
| D/C | 0.9836 | likely_pathogenic | 0.9202 | pathogenic | -0.14 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | I |
| D/E | 0.6418 | likely_pathogenic | 0.3357 | benign | -0.255 | Destabilizing | 0.966 | D | 0.39 | neutral | N | 0.459271075 | None | None | I |
| D/F | 0.9683 | likely_pathogenic | 0.9005 | pathogenic | 0.012 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | I |
| D/G | 0.7083 | likely_pathogenic | 0.3919 | ambiguous | -0.421 | Destabilizing | 0.995 | D | 0.513 | neutral | N | 0.496117309 | None | None | I |
| D/H | 0.9039 | likely_pathogenic | 0.6947 | pathogenic | 0.303 | Stabilizing | 1.0 | D | 0.567 | neutral | N | 0.496117309 | None | None | I |
| D/I | 0.9578 | likely_pathogenic | 0.818 | pathogenic | 0.313 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| D/K | 0.9448 | likely_pathogenic | 0.7689 | pathogenic | 0.245 | Stabilizing | 1.0 | D | 0.547 | neutral | None | None | None | None | I |
| D/L | 0.9272 | likely_pathogenic | 0.76 | pathogenic | 0.313 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| D/M | 0.9817 | likely_pathogenic | 0.9191 | pathogenic | 0.284 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | I |
| D/N | 0.5127 | ambiguous | 0.2395 | benign | -0.148 | Destabilizing | 0.991 | D | 0.486 | neutral | N | 0.484782808 | None | None | I |
| D/P | 0.9653 | likely_pathogenic | 0.8621 | pathogenic | 0.162 | Stabilizing | 0.994 | D | 0.593 | neutral | None | None | None | None | I |
| D/Q | 0.9036 | likely_pathogenic | 0.6782 | pathogenic | -0.074 | Destabilizing | 1.0 | D | 0.539 | neutral | None | None | None | None | I |
| D/R | 0.9304 | likely_pathogenic | 0.765 | pathogenic | 0.521 | Stabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | I |
| D/S | 0.6002 | likely_pathogenic | 0.2774 | benign | -0.26 | Destabilizing | 0.929 | D | 0.247 | neutral | None | None | None | None | I |
| D/T | 0.8358 | likely_pathogenic | 0.5517 | ambiguous | -0.083 | Destabilizing | 0.987 | D | 0.546 | neutral | None | None | None | None | I |
| D/V | 0.8894 | likely_pathogenic | 0.6425 | pathogenic | 0.162 | Stabilizing | 0.999 | D | 0.653 | neutral | N | 0.500600409 | None | None | I |
| D/W | 0.9939 | likely_pathogenic | 0.9811 | pathogenic | 0.165 | Stabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| D/Y | 0.868 | likely_pathogenic | 0.6664 | pathogenic | 0.256 | Stabilizing | 1.0 | D | 0.625 | neutral | N | 0.490492176 | 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.