Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28359 | 85300;85301;85302 | chr2:178561057;178561056;178561055 | chr2:179425784;179425783;179425782 |
| N2AB | 26718 | 80377;80378;80379 | chr2:178561057;178561056;178561055 | chr2:179425784;179425783;179425782 |
| N2A | 25791 | 77596;77597;77598 | chr2:178561057;178561056;178561055 | chr2:179425784;179425783;179425782 |
| N2B | 19294 | 58105;58106;58107 | chr2:178561057;178561056;178561055 | chr2:179425784;179425783;179425782 |
| Novex-1 | 19419 | 58480;58481;58482 | chr2:178561057;178561056;178561055 | chr2:179425784;179425783;179425782 |
| Novex-2 | 19486 | 58681;58682;58683 | chr2:178561057;178561056;178561055 | chr2:179425784;179425783;179425782 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs773774387  |
0.112 | 0.007 | N | 0.137 | 0.083 | 0.313210971179 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs773774387 |
0.112 | 0.007 | N | 0.137 | 0.083 | 0.313210971179 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs773774387 |
0.112 | 0.007 | N | 0.137 | 0.083 | 0.313210971179 | gnomAD-4.0.0 | 1.59109E-06 | None | None | None | None | I | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs763428327 |
1.01 | 0.213 | N | 0.304 | 0.351 | 0.570965073944 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/R | rs763428327 |
1.01 | 0.213 | N | 0.304 | 0.351 | 0.570965073944 | gnomAD-4.0.0 | 6.84172E-07 | None | None | None | None | I | None | 0 | 2.23614E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | None | None | 0.351 | N | 0.27 | 0.313 | 0.713738877976 | gnomAD-4.0.0 | 2.05252E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69832E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.8355 | likely_pathogenic | 0.811 | pathogenic | -1.915 | Destabilizing | 0.129 | N | 0.289 | neutral | None | None | None | None | I |
| M/C | 0.9293 | likely_pathogenic | 0.9287 | pathogenic | -1.305 | Destabilizing | 0.983 | D | 0.257 | neutral | None | None | None | None | I |
| M/D | 0.9893 | likely_pathogenic | 0.9871 | pathogenic | -0.514 | Destabilizing | 0.716 | D | 0.406 | neutral | None | None | None | None | I |
| M/E | 0.9506 | likely_pathogenic | 0.9409 | pathogenic | -0.456 | Destabilizing | 0.264 | N | 0.325 | neutral | None | None | None | None | I |
| M/F | 0.5405 | ambiguous | 0.5687 | pathogenic | -0.828 | Destabilizing | 0.418 | N | 0.215 | neutral | None | None | None | None | I |
| M/G | 0.9388 | likely_pathogenic | 0.9266 | pathogenic | -2.255 | Highly Destabilizing | 0.418 | N | 0.365 | neutral | None | None | None | None | I |
| M/H | 0.9611 | likely_pathogenic | 0.9599 | pathogenic | -1.217 | Destabilizing | 0.951 | D | 0.313 | neutral | None | None | None | None | I |
| M/I | 0.6507 | likely_pathogenic | 0.6239 | pathogenic | -1.019 | Destabilizing | 0.007 | N | 0.137 | neutral | N | 0.45722806 | None | None | I |
| M/K | 0.8386 | likely_pathogenic | 0.8243 | pathogenic | -0.659 | Destabilizing | 0.002 | N | 0.235 | neutral | N | 0.487117453 | None | None | I |
| M/L | 0.148 | likely_benign | 0.1439 | benign | -1.019 | Destabilizing | None | N | 0.079 | neutral | N | 0.409396828 | None | None | I |
| M/N | 0.9579 | likely_pathogenic | 0.9471 | pathogenic | -0.587 | Destabilizing | 0.716 | D | 0.371 | neutral | None | None | None | None | I |
| M/P | 0.9648 | likely_pathogenic | 0.963 | pathogenic | -1.292 | Destabilizing | 0.836 | D | 0.363 | neutral | None | None | None | None | I |
| M/Q | 0.8426 | likely_pathogenic | 0.8275 | pathogenic | -0.604 | Destabilizing | 0.557 | D | 0.235 | neutral | None | None | None | None | I |
| M/R | 0.8413 | likely_pathogenic | 0.8237 | pathogenic | -0.208 | Destabilizing | 0.213 | N | 0.304 | neutral | N | 0.487624432 | None | None | I |
| M/S | 0.927 | likely_pathogenic | 0.9066 | pathogenic | -1.231 | Destabilizing | 0.264 | N | 0.273 | neutral | None | None | None | None | I |
| M/T | 0.7122 | likely_pathogenic | 0.6597 | pathogenic | -1.048 | Destabilizing | 0.351 | N | 0.27 | neutral | N | 0.485850005 | None | None | I |
| M/V | 0.2361 | likely_benign | 0.2175 | benign | -1.292 | Destabilizing | 0.047 | N | 0.163 | neutral | D | 0.529530876 | None | None | I |
| M/W | 0.8786 | likely_pathogenic | 0.8851 | pathogenic | -0.748 | Destabilizing | 0.983 | D | 0.281 | neutral | None | None | None | None | I |
| M/Y | 0.9047 | likely_pathogenic | 0.9126 | pathogenic | -0.801 | Destabilizing | 0.836 | D | 0.301 | 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.