Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23484 | 70675;70676;70677 | chr2:178575682;178575681;178575680 | chr2:179440409;179440408;179440407 |
| N2AB | 21843 | 65752;65753;65754 | chr2:178575682;178575681;178575680 | chr2:179440409;179440408;179440407 |
| N2A | 20916 | 62971;62972;62973 | chr2:178575682;178575681;178575680 | chr2:179440409;179440408;179440407 |
| N2B | 14419 | 43480;43481;43482 | chr2:178575682;178575681;178575680 | chr2:179440409;179440408;179440407 |
| Novex-1 | 14544 | 43855;43856;43857 | chr2:178575682;178575681;178575680 | chr2:179440409;179440408;179440407 |
| Novex-2 | 14611 | 44056;44057;44058 | chr2:178575682;178575681;178575680 | chr2:179440409;179440408;179440407 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs1178437079  |
-0.547 | 0.65 | N | 0.463 | 0.173 | 0.353125101423 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| T/K | rs1178437079 |
-0.547 | 0.65 | N | 0.463 | 0.173 | 0.353125101423 | gnomAD-4.0.0 | 6.84284E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52283E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | None | None | 0.972 | N | 0.533 | 0.312 | 0.427940940899 | gnomAD-4.0.0 | 6.84284E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99546E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0856 | likely_benign | 0.0826 | benign | -0.676 | Destabilizing | 0.051 | N | 0.373 | neutral | N | 0.474056021 | None | None | N |
| T/C | 0.4703 | ambiguous | 0.4559 | ambiguous | -0.382 | Destabilizing | 0.993 | D | 0.521 | neutral | None | None | None | None | N |
| T/D | 0.8044 | likely_pathogenic | 0.7823 | pathogenic | -0.153 | Destabilizing | 0.92 | D | 0.51 | neutral | None | None | None | None | N |
| T/E | 0.6494 | likely_pathogenic | 0.6359 | pathogenic | -0.203 | Destabilizing | 0.781 | D | 0.482 | neutral | None | None | None | None | N |
| T/F | 0.4498 | ambiguous | 0.4247 | ambiguous | -0.959 | Destabilizing | 0.958 | D | 0.551 | neutral | None | None | None | None | N |
| T/G | 0.4312 | ambiguous | 0.3919 | ambiguous | -0.868 | Destabilizing | 0.9 | D | 0.49 | neutral | None | None | None | None | N |
| T/H | 0.5463 | ambiguous | 0.5156 | ambiguous | -1.171 | Destabilizing | 0.995 | D | 0.546 | neutral | None | None | None | None | N |
| T/I | 0.1613 | likely_benign | 0.1654 | benign | -0.272 | Destabilizing | 0.277 | N | 0.441 | neutral | N | 0.503917568 | None | None | N |
| T/K | 0.5344 | ambiguous | 0.4973 | ambiguous | -0.643 | Destabilizing | 0.65 | D | 0.463 | neutral | N | 0.516884078 | None | None | N |
| T/L | 0.117 | likely_benign | 0.1074 | benign | -0.272 | Destabilizing | 0.149 | N | 0.416 | neutral | None | None | None | None | N |
| T/M | 0.0998 | likely_benign | 0.1009 | benign | 0.074 | Stabilizing | 0.182 | N | 0.356 | neutral | None | None | None | None | N |
| T/N | 0.2884 | likely_benign | 0.2599 | benign | -0.456 | Destabilizing | 0.79 | D | 0.447 | neutral | None | None | None | None | N |
| T/P | 0.1644 | likely_benign | 0.1457 | benign | -0.377 | Destabilizing | 0.896 | D | 0.525 | neutral | N | 0.520905818 | None | None | N |
| T/Q | 0.4372 | ambiguous | 0.4132 | ambiguous | -0.72 | Destabilizing | 0.891 | D | 0.536 | neutral | None | None | None | None | N |
| T/R | 0.4799 | ambiguous | 0.4393 | ambiguous | -0.312 | Destabilizing | 0.972 | D | 0.533 | neutral | N | 0.50522429 | None | None | N |
| T/S | 0.1804 | likely_benign | 0.1696 | benign | -0.707 | Destabilizing | 0.115 | N | 0.381 | neutral | N | 0.501837268 | None | None | N |
| T/V | 0.107 | likely_benign | 0.1079 | benign | -0.377 | Destabilizing | 0.01 | N | 0.114 | neutral | None | None | None | None | N |
| T/W | 0.8335 | likely_pathogenic | 0.8288 | pathogenic | -0.886 | Destabilizing | 0.998 | D | 0.586 | neutral | None | None | None | None | N |
| T/Y | 0.5584 | ambiguous | 0.5444 | ambiguous | -0.654 | Destabilizing | 0.979 | D | 0.563 | 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.