Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26767 | 80524;80525;80526 | chr2:178565833;178565832;178565831 | chr2:179430560;179430559;179430558 |
| N2AB | 25126 | 75601;75602;75603 | chr2:178565833;178565832;178565831 | chr2:179430560;179430559;179430558 |
| N2A | 24199 | 72820;72821;72822 | chr2:178565833;178565832;178565831 | chr2:179430560;179430559;179430558 |
| N2B | 17702 | 53329;53330;53331 | chr2:178565833;178565832;178565831 | chr2:179430560;179430559;179430558 |
| Novex-1 | 17827 | 53704;53705;53706 | chr2:178565833;178565832;178565831 | chr2:179430560;179430559;179430558 |
| Novex-2 | 17894 | 53905;53906;53907 | chr2:178565833;178565832;178565831 | chr2:179430560;179430559;179430558 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs1559345492  |
None | 0.166 | N | 0.415 | 0.066 | 0.369495900351 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| V/I | rs1559345492 |
None | 0.166 | N | 0.415 | 0.066 | 0.369495900351 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs1559345492 |
None | 0.166 | N | 0.415 | 0.066 | 0.369495900351 | gnomAD-4.0.0 | 1.8593E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5431E-06 | 0 | 0 |
| V/L | None | None | 0.003 | N | 0.179 | 0.068 | 0.340273420219 | gnomAD-4.0.0 | 6.84277E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1218 | likely_benign | 0.1371 | benign | -1.443 | Destabilizing | 0.001 | N | 0.156 | neutral | N | 0.430144954 | None | None | I |
| V/C | 0.5462 | ambiguous | 0.5763 | pathogenic | -0.858 | Destabilizing | 0.972 | D | 0.493 | neutral | None | None | None | None | I |
| V/D | 0.2413 | likely_benign | 0.2562 | benign | -1.426 | Destabilizing | 0.326 | N | 0.471 | neutral | N | 0.416735727 | None | None | I |
| V/E | 0.1944 | likely_benign | 0.2118 | benign | -1.468 | Destabilizing | 0.017 | N | 0.342 | neutral | None | None | None | None | I |
| V/F | 0.1297 | likely_benign | 0.1326 | benign | -1.222 | Destabilizing | 0.772 | D | 0.506 | neutral | N | 0.473642828 | None | None | I |
| V/G | 0.1834 | likely_benign | 0.2021 | benign | -1.709 | Destabilizing | 0.326 | N | 0.473 | neutral | N | 0.461779544 | None | None | I |
| V/H | 0.4173 | ambiguous | 0.459 | ambiguous | -1.209 | Destabilizing | 0.901 | D | 0.527 | neutral | None | None | None | None | I |
| V/I | 0.065 | likely_benign | 0.0702 | benign | -0.829 | Destabilizing | 0.166 | N | 0.415 | neutral | N | 0.498428817 | None | None | I |
| V/K | 0.2773 | likely_benign | 0.3168 | benign | -1.256 | Destabilizing | 0.39 | N | 0.454 | neutral | None | None | None | None | I |
| V/L | 0.0946 | likely_benign | 0.1013 | benign | -0.829 | Destabilizing | 0.003 | N | 0.179 | neutral | N | 0.39584038 | None | None | I |
| V/M | 0.0914 | likely_benign | 0.0999 | benign | -0.55 | Destabilizing | 0.818 | D | 0.511 | neutral | None | None | None | None | I |
| V/N | 0.1514 | likely_benign | 0.1777 | benign | -0.982 | Destabilizing | 0.901 | D | 0.524 | neutral | None | None | None | None | I |
| V/P | 0.3398 | likely_benign | 0.382 | ambiguous | -0.999 | Destabilizing | 0.004 | N | 0.345 | neutral | None | None | None | None | I |
| V/Q | 0.212 | likely_benign | 0.2417 | benign | -1.232 | Destabilizing | 0.047 | N | 0.351 | neutral | None | None | None | None | I |
| V/R | 0.2887 | likely_benign | 0.3175 | benign | -0.609 | Destabilizing | 0.818 | D | 0.514 | neutral | None | None | None | None | I |
| V/S | 0.1382 | likely_benign | 0.1598 | benign | -1.413 | Destabilizing | 0.39 | N | 0.475 | neutral | None | None | None | None | I |
| V/T | 0.1319 | likely_benign | 0.1546 | benign | -1.362 | Destabilizing | 0.561 | D | 0.325 | neutral | None | None | None | None | I |
| V/W | 0.705 | likely_pathogenic | 0.7201 | pathogenic | -1.361 | Destabilizing | 0.991 | D | 0.568 | neutral | None | None | None | None | I |
| V/Y | 0.376 | ambiguous | 0.405 | ambiguous | -1.111 | Destabilizing | 0.965 | D | 0.509 | 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.