Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20877 | 62854;62855;62856 | chr2:178589096;178589095;178589094 | chr2:179453823;179453822;179453821 |
| N2AB | 19236 | 57931;57932;57933 | chr2:178589096;178589095;178589094 | chr2:179453823;179453822;179453821 |
| N2A | 18309 | 55150;55151;55152 | chr2:178589096;178589095;178589094 | chr2:179453823;179453822;179453821 |
| N2B | 11812 | 35659;35660;35661 | chr2:178589096;178589095;178589094 | chr2:179453823;179453822;179453821 |
| Novex-1 | 11937 | 36034;36035;36036 | chr2:178589096;178589095;178589094 | chr2:179453823;179453822;179453821 |
| Novex-2 | 12004 | 36235;36236;36237 | chr2:178589096;178589095;178589094 | chr2:179453823;179453822;179453821 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1406472135  |
-0.259 | 0.002 | N | 0.365 | 0.232 | 0.289474373501 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/C | rs1406472135 |
-0.259 | 0.002 | N | 0.365 | 0.232 | 0.289474373501 | gnomAD-4.0.0 | 4.79825E-06 | None | None | None | None | N | None | 0 | 2.28864E-05 | None | 0 | 0 | None | 0 | 0 | 5.71899E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1271 | likely_benign | 0.1076 | benign | -0.171 | Destabilizing | 0.027 | N | 0.397 | neutral | N | 0.507035231 | None | None | N |
| S/C | 0.1425 | likely_benign | 0.09 | benign | -0.541 | Destabilizing | 0.002 | N | 0.365 | neutral | N | 0.498719886 | None | None | N |
| S/D | 0.6766 | likely_pathogenic | 0.6142 | pathogenic | -1.728 | Destabilizing | 0.081 | N | 0.347 | neutral | None | None | None | None | N |
| S/E | 0.8092 | likely_pathogenic | 0.779 | pathogenic | -1.716 | Destabilizing | 0.149 | N | 0.389 | neutral | None | None | None | None | N |
| S/F | 0.3304 | likely_benign | 0.2437 | benign | -0.618 | Destabilizing | 0.484 | N | 0.398 | neutral | N | 0.476007275 | None | None | N |
| S/G | 0.1226 | likely_benign | 0.085 | benign | -0.386 | Destabilizing | None | N | 0.071 | neutral | None | None | None | None | N |
| S/H | 0.4744 | ambiguous | 0.4029 | ambiguous | -1.068 | Destabilizing | 0.698 | D | 0.364 | neutral | None | None | None | None | N |
| S/I | 0.4211 | ambiguous | 0.3235 | benign | 0.284 | Stabilizing | 0.38 | N | 0.391 | neutral | None | None | None | None | N |
| S/K | 0.8537 | likely_pathogenic | 0.8052 | pathogenic | -0.641 | Destabilizing | 0.081 | N | 0.389 | neutral | None | None | None | None | N |
| S/L | 0.202 | likely_benign | 0.1629 | benign | 0.284 | Stabilizing | 0.081 | N | 0.374 | neutral | None | None | None | None | N |
| S/M | 0.3189 | likely_benign | 0.2453 | benign | 0.587 | Stabilizing | 0.935 | D | 0.363 | neutral | None | None | None | None | N |
| S/N | 0.2631 | likely_benign | 0.1937 | benign | -0.991 | Destabilizing | 0.001 | N | 0.258 | neutral | None | None | None | None | N |
| S/P | 0.9196 | likely_pathogenic | 0.8989 | pathogenic | 0.165 | Stabilizing | 0.484 | N | 0.359 | neutral | N | 0.491883031 | None | None | N |
| S/Q | 0.679 | likely_pathogenic | 0.5988 | pathogenic | -1.233 | Destabilizing | 0.38 | N | 0.382 | neutral | None | None | None | None | N |
| S/R | 0.7907 | likely_pathogenic | 0.7258 | pathogenic | -0.493 | Destabilizing | 0.38 | N | 0.355 | neutral | None | None | None | None | N |
| S/T | 0.1004 | likely_benign | 0.083 | benign | -0.688 | Destabilizing | None | N | 0.245 | neutral | N | 0.435630919 | None | None | N |
| S/V | 0.3711 | ambiguous | 0.2779 | benign | 0.165 | Stabilizing | 0.081 | N | 0.367 | neutral | None | None | None | None | N |
| S/W | 0.5693 | likely_pathogenic | 0.4814 | ambiguous | -0.803 | Destabilizing | 0.935 | D | 0.501 | neutral | None | None | None | None | N |
| S/Y | 0.3286 | likely_benign | 0.2604 | benign | -0.38 | Destabilizing | 0.741 | D | 0.398 | neutral | N | 0.474993317 | None | None | N |
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.