Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27784 | 83575;83576;83577 | chr2:178562782;178562781;178562780 | chr2:179427509;179427508;179427507 |
| N2AB | 26143 | 78652;78653;78654 | chr2:178562782;178562781;178562780 | chr2:179427509;179427508;179427507 |
| N2A | 25216 | 75871;75872;75873 | chr2:178562782;178562781;178562780 | chr2:179427509;179427508;179427507 |
| N2B | 18719 | 56380;56381;56382 | chr2:178562782;178562781;178562780 | chr2:179427509;179427508;179427507 |
| Novex-1 | 18844 | 56755;56756;56757 | chr2:178562782;178562781;178562780 | chr2:179427509;179427508;179427507 |
| Novex-2 | 18911 | 56956;56957;56958 | chr2:178562782;178562781;178562780 | chr2:179427509;179427508;179427507 |
| 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 | None | None | 0.365 | N | 0.482 | 0.215 | 0.170165803431 | gnomAD-4.0.0 | 6.84433E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99586E-07 | 0 | 0 |
| T/M | rs140879454  |
-0.463 | 0.899 | N | 0.577 | 0.194 | None | gnomAD-2.1.1 | 3.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.81278E-04 | None | 9.81E-05 | None | 0 | 0 | 1.67112E-04 |
| T/M | rs140879454 |
-0.463 | 0.899 | N | 0.577 | 0.194 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.86698E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/M | rs140879454 |
-0.463 | 0.899 | N | 0.577 | 0.194 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| T/M | rs140879454 |
-0.463 | 0.899 | N | 0.577 | 0.194 | None | gnomAD-4.0.0 | 1.36366E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.78859E-04 | None | 0 | 0 | 5.93404E-06 | 5.49089E-05 | 3.20307E-05 |
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 | 0.0967 | likely_benign | 0.1023 | benign | -1.246 | Destabilizing | 0.003 | N | 0.307 | neutral | N | 0.480727308 | None | None | N |
| T/C | 0.2558 | likely_benign | 0.2767 | benign | -1.198 | Destabilizing | 0.973 | D | 0.561 | neutral | None | None | None | None | N |
| T/D | 0.57 | likely_pathogenic | 0.6133 | pathogenic | -1.659 | Destabilizing | 0.114 | N | 0.463 | neutral | None | None | None | None | N |
| T/E | 0.4809 | ambiguous | 0.5208 | ambiguous | -1.512 | Destabilizing | 0.176 | N | 0.46 | neutral | None | None | None | None | N |
| T/F | 0.1235 | likely_benign | 0.1325 | benign | -0.958 | Destabilizing | 0.849 | D | 0.559 | neutral | None | None | None | None | N |
| T/G | 0.2842 | likely_benign | 0.3112 | benign | -1.602 | Destabilizing | 0.518 | D | 0.501 | neutral | None | None | None | None | N |
| T/H | 0.2549 | likely_benign | 0.2671 | benign | -1.669 | Destabilizing | 0.81 | D | 0.573 | neutral | None | None | None | None | N |
| T/I | 0.0745 | likely_benign | 0.0832 | benign | -0.337 | Destabilizing | 0.001 | N | 0.333 | neutral | None | None | None | None | N |
| T/K | 0.3995 | ambiguous | 0.4221 | ambiguous | -0.856 | Destabilizing | 0.365 | N | 0.482 | neutral | N | 0.482297471 | None | None | N |
| T/L | 0.0637 | likely_benign | 0.0696 | benign | -0.337 | Destabilizing | 0.041 | N | 0.411 | neutral | None | None | None | None | N |
| T/M | 0.0691 | likely_benign | 0.0713 | benign | -0.368 | Destabilizing | 0.899 | D | 0.577 | neutral | N | 0.491691993 | None | None | N |
| T/N | 0.1427 | likely_benign | 0.1492 | benign | -1.362 | Destabilizing | 0.114 | N | 0.485 | neutral | None | None | None | None | N |
| T/P | 0.6453 | likely_pathogenic | 0.6871 | pathogenic | -0.61 | Destabilizing | 0.408 | N | 0.557 | neutral | D | 0.524292879 | None | None | N |
| T/Q | 0.2926 | likely_benign | 0.2976 | benign | -1.321 | Destabilizing | 0.025 | N | 0.368 | neutral | None | None | None | None | N |
| T/R | 0.3438 | ambiguous | 0.369 | ambiguous | -0.824 | Destabilizing | 0.915 | D | 0.56 | neutral | N | 0.481537002 | None | None | N |
| T/S | 0.1029 | likely_benign | 0.1077 | benign | -1.569 | Destabilizing | 0.001 | N | 0.254 | neutral | N | 0.476576251 | None | None | N |
| T/V | 0.0722 | likely_benign | 0.0783 | benign | -0.61 | Destabilizing | 0.001 | N | 0.227 | neutral | None | None | None | None | N |
| T/W | 0.4632 | ambiguous | 0.4802 | ambiguous | -1.018 | Destabilizing | 0.992 | D | 0.611 | neutral | None | None | None | None | N |
| T/Y | 0.19 | likely_benign | 0.198 | benign | -0.688 | Destabilizing | 0.919 | D | 0.555 | 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.