Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26544 | 79855;79856;79857 | chr2:178566502;178566501;178566500 | chr2:179431229;179431228;179431227 |
| N2AB | 24903 | 74932;74933;74934 | chr2:178566502;178566501;178566500 | chr2:179431229;179431228;179431227 |
| N2A | 23976 | 72151;72152;72153 | chr2:178566502;178566501;178566500 | chr2:179431229;179431228;179431227 |
| N2B | 17479 | 52660;52661;52662 | chr2:178566502;178566501;178566500 | chr2:179431229;179431228;179431227 |
| Novex-1 | 17604 | 53035;53036;53037 | chr2:178566502;178566501;178566500 | chr2:179431229;179431228;179431227 |
| Novex-2 | 17671 | 53236;53237;53238 | chr2:178566502;178566501;178566500 | chr2:179431229;179431228;179431227 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs1008452641  |
0.006 | None | N | 0.184 | 0.12 | 0.110078149338 | 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 |
| R/K | rs1008452641 |
0.006 | None | N | 0.184 | 0.12 | 0.110078149338 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/K | rs1008452641 |
0.006 | None | N | 0.184 | 0.12 | 0.110078149338 | gnomAD-4.0.0 | 3.09919E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54306E-06 | 2.19563E-05 | 0 |
| R/S | rs1309466474 |
-0.244 | 0.002 | N | 0.285 | 0.074 | 0.167679373172 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/S | rs1309466474 |
-0.244 | 0.002 | N | 0.285 | 0.074 | 0.167679373172 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85883E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2243 | likely_benign | 0.2357 | benign | -0.112 | Destabilizing | 0.016 | N | 0.381 | neutral | None | None | None | None | I |
| R/C | 0.1783 | likely_benign | 0.1559 | benign | -0.367 | Destabilizing | 0.864 | D | 0.438 | neutral | None | None | None | None | I |
| R/D | 0.4555 | ambiguous | 0.4915 | ambiguous | -0.127 | Destabilizing | 0.016 | N | 0.476 | neutral | None | None | None | None | I |
| R/E | 0.2586 | likely_benign | 0.2769 | benign | -0.073 | Destabilizing | 0.016 | N | 0.405 | neutral | None | None | None | None | I |
| R/F | 0.4484 | ambiguous | 0.4698 | ambiguous | -0.383 | Destabilizing | 0.628 | D | 0.465 | neutral | None | None | None | None | I |
| R/G | 0.1614 | likely_benign | 0.1731 | benign | -0.284 | Destabilizing | 0.024 | N | 0.435 | neutral | N | 0.467886064 | None | None | I |
| R/H | 0.1027 | likely_benign | 0.1004 | benign | -0.67 | Destabilizing | 0.356 | N | 0.533 | neutral | None | None | None | None | I |
| R/I | 0.2385 | likely_benign | 0.2342 | benign | 0.3 | Stabilizing | 0.295 | N | 0.516 | neutral | N | 0.481484096 | None | None | I |
| R/K | 0.0725 | likely_benign | 0.0838 | benign | -0.227 | Destabilizing | None | N | 0.184 | neutral | N | 0.439172656 | None | None | I |
| R/L | 0.1769 | likely_benign | 0.1812 | benign | 0.3 | Stabilizing | 0.072 | N | 0.499 | neutral | None | None | None | None | I |
| R/M | 0.2019 | likely_benign | 0.2211 | benign | -0.093 | Destabilizing | 0.628 | D | 0.5 | neutral | None | None | None | None | I |
| R/N | 0.3265 | likely_benign | 0.3637 | ambiguous | -0.064 | Destabilizing | None | N | 0.203 | neutral | None | None | None | None | I |
| R/P | 0.2181 | likely_benign | 0.2308 | benign | 0.182 | Stabilizing | 0.136 | N | 0.583 | neutral | None | None | None | None | I |
| R/Q | 0.0906 | likely_benign | 0.0943 | benign | -0.164 | Destabilizing | 0.001 | N | 0.298 | neutral | None | None | None | None | I |
| R/S | 0.2976 | likely_benign | 0.3185 | benign | -0.425 | Destabilizing | 0.002 | N | 0.285 | neutral | N | 0.470935571 | None | None | I |
| R/T | 0.158 | likely_benign | 0.1629 | benign | -0.244 | Destabilizing | 0.024 | N | 0.469 | neutral | N | 0.469009987 | None | None | I |
| R/V | 0.2624 | likely_benign | 0.2727 | benign | 0.182 | Stabilizing | 0.072 | N | 0.583 | neutral | None | None | None | None | I |
| R/W | 0.1779 | likely_benign | 0.1744 | benign | -0.443 | Destabilizing | 0.864 | D | 0.451 | neutral | None | None | None | None | I |
| R/Y | 0.3215 | likely_benign | 0.3279 | benign | -0.039 | Destabilizing | 0.356 | N | 0.483 | 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.