Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29540 | 88843;88844;88845 | chr2:178554729;178554728;178554727 | chr2:179419456;179419455;179419454 |
| N2AB | 27899 | 83920;83921;83922 | chr2:178554729;178554728;178554727 | chr2:179419456;179419455;179419454 |
| N2A | 26972 | 81139;81140;81141 | chr2:178554729;178554728;178554727 | chr2:179419456;179419455;179419454 |
| N2B | 20475 | 61648;61649;61650 | chr2:178554729;178554728;178554727 | chr2:179419456;179419455;179419454 |
| Novex-1 | 20600 | 62023;62024;62025 | chr2:178554729;178554728;178554727 | chr2:179419456;179419455;179419454 |
| Novex-2 | 20667 | 62224;62225;62226 | chr2:178554729;178554728;178554727 | chr2:179419456;179419455;179419454 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.012 | N | 0.31 | 0.301 | 0.513901218509 | gnomAD-4.0.0 | 4.78947E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29609E-06 | 0 | 0 |
| P/R | rs747863143  |
0.212 | 0.934 | N | 0.513 | 0.358 | 0.499600832404 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/R | rs747863143 |
0.212 | 0.934 | N | 0.513 | 0.358 | 0.499600832404 | gnomAD-4.0.0 | 3.42105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59776E-06 | 1.16007E-05 | 0 |
| P/T | rs1342421251 |
-0.394 | 0.891 | N | 0.427 | 0.349 | 0.415313616471 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.34E-05 | 0 |
| P/T | rs1342421251 |
-0.394 | 0.891 | N | 0.427 | 0.349 | 0.415313616471 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 1.09649E-03 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs1342421251 |
-0.394 | 0.891 | N | 0.427 | 0.349 | 0.415313616471 | gnomAD-4.0.0 | 4.95782E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93311E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.125 | likely_benign | 0.137 | benign | -0.499 | Destabilizing | 0.625 | D | 0.411 | neutral | N | 0.498791883 | None | None | N |
| P/C | 0.468 | ambiguous | 0.5101 | ambiguous | -0.796 | Destabilizing | 0.998 | D | 0.601 | neutral | None | None | None | None | N |
| P/D | 0.3913 | ambiguous | 0.4198 | ambiguous | -0.109 | Destabilizing | 0.728 | D | 0.378 | neutral | None | None | None | None | N |
| P/E | 0.2967 | likely_benign | 0.3344 | benign | -0.2 | Destabilizing | 0.029 | N | 0.151 | neutral | None | None | None | None | N |
| P/F | 0.5171 | ambiguous | 0.5907 | pathogenic | -0.571 | Destabilizing | 0.949 | D | 0.563 | neutral | None | None | None | None | N |
| P/G | 0.3714 | ambiguous | 0.4087 | ambiguous | -0.642 | Destabilizing | 0.915 | D | 0.44 | neutral | None | None | None | None | N |
| P/H | 0.2291 | likely_benign | 0.2602 | benign | -0.068 | Destabilizing | 0.998 | D | 0.527 | neutral | None | None | None | None | N |
| P/I | 0.3554 | ambiguous | 0.4183 | ambiguous | -0.265 | Destabilizing | 0.904 | D | 0.479 | neutral | None | None | None | None | N |
| P/K | 0.2664 | likely_benign | 0.2934 | benign | -0.466 | Destabilizing | 0.842 | D | 0.373 | neutral | None | None | None | None | N |
| P/L | 0.1697 | likely_benign | 0.1955 | benign | -0.265 | Destabilizing | 0.012 | N | 0.31 | neutral | N | 0.487201179 | None | None | N |
| P/M | 0.3497 | ambiguous | 0.3993 | ambiguous | -0.495 | Destabilizing | 0.949 | D | 0.531 | neutral | None | None | None | None | N |
| P/N | 0.3145 | likely_benign | 0.3566 | ambiguous | -0.292 | Destabilizing | 0.974 | D | 0.517 | neutral | None | None | None | None | N |
| P/Q | 0.1933 | likely_benign | 0.2176 | benign | -0.484 | Destabilizing | 0.934 | D | 0.468 | neutral | N | 0.497666248 | None | None | N |
| P/R | 0.2004 | likely_benign | 0.2192 | benign | 0.022 | Stabilizing | 0.934 | D | 0.513 | neutral | N | 0.505148212 | None | None | N |
| P/S | 0.19 | likely_benign | 0.2128 | benign | -0.704 | Destabilizing | 0.801 | D | 0.381 | neutral | N | 0.478396677 | None | None | N |
| P/T | 0.1567 | likely_benign | 0.1793 | benign | -0.688 | Destabilizing | 0.891 | D | 0.427 | neutral | N | 0.497159269 | None | None | N |
| P/V | 0.2577 | likely_benign | 0.3001 | benign | -0.309 | Destabilizing | 0.728 | D | 0.435 | neutral | None | None | None | None | N |
| P/W | 0.7093 | likely_pathogenic | 0.7507 | pathogenic | -0.633 | Destabilizing | 0.998 | D | 0.696 | prob.neutral | None | None | None | None | N |
| P/Y | 0.4892 | ambiguous | 0.5541 | ambiguous | -0.355 | Destabilizing | 0.991 | D | 0.562 | 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.