Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26442 | 79549;79550;79551 | chr2:178566808;178566807;178566806 | chr2:179431535;179431534;179431533 |
| N2AB | 24801 | 74626;74627;74628 | chr2:178566808;178566807;178566806 | chr2:179431535;179431534;179431533 |
| N2A | 23874 | 71845;71846;71847 | chr2:178566808;178566807;178566806 | chr2:179431535;179431534;179431533 |
| N2B | 17377 | 52354;52355;52356 | chr2:178566808;178566807;178566806 | chr2:179431535;179431534;179431533 |
| Novex-1 | 17502 | 52729;52730;52731 | chr2:178566808;178566807;178566806 | chr2:179431535;179431534;179431533 |
| Novex-2 | 17569 | 52930;52931;52932 | chr2:178566808;178566807;178566806 | chr2:179431535;179431534;179431533 |
| 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/I | rs1288656149  |
0.028 | 0.994 | N | 0.684 | 0.51 | 0.509762279564 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs1288656149 |
0.028 | 0.994 | N | 0.684 | 0.51 | 0.509762279564 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| T/I | rs1288656149 |
0.028 | 0.994 | N | 0.684 | 0.51 | 0.509762279564 | gnomAD-4.0.0 | 2.56379E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.67996E-05 | 0 |
| T/R | None | None | 0.994 | N | 0.684 | 0.457 | 0.584086171949 | gnomAD-4.0.0 | 1.59234E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77747E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1042 | likely_benign | 0.1307 | benign | -0.556 | Destabilizing | 0.958 | D | 0.371 | neutral | N | 0.489988266 | None | None | I |
| T/C | 0.4398 | ambiguous | 0.5352 | ambiguous | -0.477 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| T/D | 0.6634 | likely_pathogenic | 0.7995 | pathogenic | 0.444 | Stabilizing | 0.995 | D | 0.623 | neutral | None | None | None | None | I |
| T/E | 0.6295 | likely_pathogenic | 0.7712 | pathogenic | 0.42 | Stabilizing | 0.991 | D | 0.633 | neutral | None | None | None | None | I |
| T/F | 0.38 | ambiguous | 0.4933 | ambiguous | -0.891 | Destabilizing | 0.998 | D | 0.684 | prob.neutral | None | None | None | None | I |
| T/G | 0.2012 | likely_benign | 0.2523 | benign | -0.739 | Destabilizing | 0.991 | D | 0.598 | neutral | None | None | None | None | I |
| T/H | 0.3733 | ambiguous | 0.5018 | ambiguous | -0.828 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| T/I | 0.3186 | likely_benign | 0.4479 | ambiguous | -0.182 | Destabilizing | 0.994 | D | 0.684 | prob.neutral | N | 0.490187964 | None | None | I |
| T/K | 0.4324 | ambiguous | 0.6008 | pathogenic | -0.304 | Destabilizing | 0.988 | D | 0.632 | neutral | N | 0.472730656 | None | None | I |
| T/L | 0.1313 | likely_benign | 0.1796 | benign | -0.182 | Destabilizing | 0.968 | D | 0.563 | neutral | None | None | None | None | I |
| T/M | 0.11 | likely_benign | 0.14 | benign | -0.24 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| T/N | 0.1563 | likely_benign | 0.221 | benign | -0.265 | Destabilizing | 0.995 | D | 0.608 | neutral | None | None | None | None | I |
| T/P | 0.1264 | likely_benign | 0.1787 | benign | -0.276 | Destabilizing | 0.067 | N | 0.318 | neutral | N | 0.497839745 | None | None | I |
| T/Q | 0.3528 | ambiguous | 0.4763 | ambiguous | -0.378 | Destabilizing | 0.995 | D | 0.692 | prob.neutral | None | None | None | None | I |
| T/R | 0.3699 | ambiguous | 0.5275 | ambiguous | -0.063 | Destabilizing | 0.994 | D | 0.684 | prob.neutral | N | 0.48500652 | None | None | I |
| T/S | 0.1073 | likely_benign | 0.1341 | benign | -0.563 | Destabilizing | 0.958 | D | 0.381 | neutral | N | 0.45997479 | None | None | I |
| T/V | 0.2108 | likely_benign | 0.2864 | benign | -0.276 | Destabilizing | 0.984 | D | 0.479 | neutral | None | None | None | None | I |
| T/W | 0.6885 | likely_pathogenic | 0.7763 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| T/Y | 0.4055 | ambiguous | 0.508 | ambiguous | -0.585 | Destabilizing | 0.998 | D | 0.68 | prob.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.