Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18535 | 55828;55829;55830 | chr2:178601394;178601393;178601392 | chr2:179466121;179466120;179466119 |
| N2AB | 16894 | 50905;50906;50907 | chr2:178601394;178601393;178601392 | chr2:179466121;179466120;179466119 |
| N2A | 15967 | 48124;48125;48126 | chr2:178601394;178601393;178601392 | chr2:179466121;179466120;179466119 |
| N2B | 9470 | 28633;28634;28635 | chr2:178601394;178601393;178601392 | chr2:179466121;179466120;179466119 |
| Novex-1 | 9595 | 29008;29009;29010 | chr2:178601394;178601393;178601392 | chr2:179466121;179466120;179466119 |
| Novex-2 | 9662 | 29209;29210;29211 | chr2:178601394;178601393;178601392 | chr2:179466121;179466120;179466119 |
| 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 | rs770105954  |
-0.425 | 0.999 | N | 0.556 | 0.363 | 0.344945010812 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs770105954 |
-0.425 | 0.999 | N | 0.556 | 0.363 | 0.344945010812 | gnomAD-4.0.0 | 3.18668E-06 | None | None | None | None | N | None | 0 | 4.57917E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.1014 | likely_benign | 0.1093 | benign | -0.704 | Destabilizing | 0.807 | D | 0.343 | neutral | None | None | None | None | N |
| S/C | 0.1448 | likely_benign | 0.1844 | benign | -0.44 | Destabilizing | 0.999 | D | 0.556 | neutral | N | 0.485322437 | None | None | N |
| S/D | 0.5724 | likely_pathogenic | 0.694 | pathogenic | 0.315 | Stabilizing | 0.976 | D | 0.448 | neutral | None | None | None | None | N |
| S/E | 0.7016 | likely_pathogenic | 0.7745 | pathogenic | 0.314 | Stabilizing | 0.976 | D | 0.441 | neutral | None | None | None | None | N |
| S/F | 0.3282 | likely_benign | 0.4282 | ambiguous | -1.129 | Destabilizing | 0.998 | D | 0.604 | neutral | None | None | None | None | N |
| S/G | 0.0838 | likely_benign | 0.1121 | benign | -0.904 | Destabilizing | 0.02 | N | 0.186 | neutral | N | 0.482656861 | None | None | N |
| S/H | 0.4286 | ambiguous | 0.5289 | ambiguous | -1.124 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| S/I | 0.2615 | likely_benign | 0.3331 | benign | -0.282 | Destabilizing | 0.997 | D | 0.589 | neutral | N | 0.468179234 | None | None | N |
| S/K | 0.7338 | likely_pathogenic | 0.8214 | pathogenic | -0.307 | Destabilizing | 0.976 | D | 0.453 | neutral | None | None | None | None | N |
| S/L | 0.1453 | likely_benign | 0.1737 | benign | -0.282 | Destabilizing | 0.993 | D | 0.518 | neutral | None | None | None | None | N |
| S/M | 0.2269 | likely_benign | 0.2493 | benign | -0.277 | Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| S/N | 0.1365 | likely_benign | 0.1741 | benign | -0.332 | Destabilizing | 0.939 | D | 0.45 | neutral | N | 0.496490163 | None | None | N |
| S/P | 0.5085 | ambiguous | 0.6223 | pathogenic | -0.392 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | N |
| S/Q | 0.5366 | ambiguous | 0.6086 | pathogenic | -0.377 | Destabilizing | 0.998 | D | 0.527 | neutral | None | None | None | None | N |
| S/R | 0.7073 | likely_pathogenic | 0.8319 | pathogenic | -0.203 | Destabilizing | 0.991 | D | 0.582 | neutral | N | 0.474613381 | None | None | N |
| S/T | 0.1025 | likely_benign | 0.1141 | benign | -0.392 | Destabilizing | 0.969 | D | 0.379 | neutral | N | 0.446999919 | None | None | N |
| S/V | 0.238 | likely_benign | 0.2869 | benign | -0.392 | Destabilizing | 0.993 | D | 0.557 | neutral | None | None | None | None | N |
| S/W | 0.5728 | likely_pathogenic | 0.7118 | pathogenic | -1.148 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | N |
| S/Y | 0.3152 | likely_benign | 0.411 | ambiguous | -0.832 | Destabilizing | 0.998 | D | 0.606 | neutral | None | None | 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.