Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27968 | 84127;84128;84129 | chr2:178562230;178562229;178562228 | chr2:179426957;179426956;179426955 |
| N2AB | 26327 | 79204;79205;79206 | chr2:178562230;178562229;178562228 | chr2:179426957;179426956;179426955 |
| N2A | 25400 | 76423;76424;76425 | chr2:178562230;178562229;178562228 | chr2:179426957;179426956;179426955 |
| N2B | 18903 | 56932;56933;56934 | chr2:178562230;178562229;178562228 | chr2:179426957;179426956;179426955 |
| Novex-1 | 19028 | 57307;57308;57309 | chr2:178562230;178562229;178562228 | chr2:179426957;179426956;179426955 |
| Novex-2 | 19095 | 57508;57509;57510 | chr2:178562230;178562229;178562228 | chr2:179426957;179426956;179426955 |
| 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/S | rs541254027  |
-0.623 | 0.183 | N | 0.413 | 0.144 | 0.263612267334 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 1.24162E-04 | 2.85E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs541254027 |
-0.623 | 0.183 | N | 0.413 | 0.144 | 0.263612267334 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 1.44816E-04 | 6.55E-05 | 0 | 0 | 1.93199E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs541254027 |
-0.623 | 0.183 | N | 0.413 | 0.144 | 0.263612267334 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| P/S | rs541254027 |
-0.623 | 0.183 | N | 0.413 | 0.144 | 0.263612267334 | gnomAD-4.0.0 | 9.30168E-06 | None | None | None | None | N | None | 1.06729E-04 | 3.34269E-05 | None | 0 | 6.70331E-05 | None | 0 | 0 | 1.69577E-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 | 0.1157 | likely_benign | 0.1206 | benign | -0.59 | Destabilizing | 0.047 | N | 0.344 | neutral | N | 0.501061769 | None | None | N |
| P/C | 0.5775 | likely_pathogenic | 0.5907 | pathogenic | -0.647 | Destabilizing | 0.94 | D | 0.505 | neutral | None | None | None | None | N |
| P/D | 0.5772 | likely_pathogenic | 0.5326 | ambiguous | -0.616 | Destabilizing | 0.418 | N | 0.473 | neutral | None | None | None | None | N |
| P/E | 0.433 | ambiguous | 0.3979 | ambiguous | -0.654 | Destabilizing | 0.264 | N | 0.437 | neutral | None | None | None | None | N |
| P/F | 0.5877 | likely_pathogenic | 0.6249 | pathogenic | -0.672 | Destabilizing | 0.264 | N | 0.575 | neutral | None | None | None | None | N |
| P/G | 0.3629 | ambiguous | 0.3846 | ambiguous | -0.739 | Destabilizing | 0.418 | N | 0.447 | neutral | None | None | None | None | N |
| P/H | 0.2571 | likely_benign | 0.2787 | benign | -0.088 | Destabilizing | 0.794 | D | 0.486 | neutral | N | 0.503102703 | None | None | N |
| P/I | 0.3391 | likely_benign | 0.3415 | ambiguous | -0.297 | Destabilizing | 0.004 | N | 0.239 | neutral | None | None | None | None | N |
| P/K | 0.4132 | ambiguous | 0.3843 | ambiguous | -0.407 | Destabilizing | 0.001 | N | 0.165 | neutral | None | None | None | None | N |
| P/L | 0.1224 | likely_benign | 0.1389 | benign | -0.297 | Destabilizing | None | N | 0.207 | neutral | N | 0.471509653 | None | None | N |
| P/M | 0.3343 | likely_benign | 0.3638 | ambiguous | -0.687 | Destabilizing | 0.027 | N | 0.287 | neutral | None | None | None | None | N |
| P/N | 0.3899 | ambiguous | 0.3756 | ambiguous | -0.304 | Destabilizing | 0.418 | N | 0.539 | neutral | None | None | None | None | N |
| P/Q | 0.2098 | likely_benign | 0.2222 | benign | -0.448 | Destabilizing | 0.418 | N | 0.494 | neutral | None | None | None | None | N |
| P/R | 0.2536 | likely_benign | 0.2686 | benign | -0.004 | Destabilizing | 0.213 | N | 0.512 | neutral | N | 0.483731 | None | None | N |
| P/S | 0.1709 | likely_benign | 0.1827 | benign | -0.617 | Destabilizing | 0.183 | N | 0.413 | neutral | N | 0.519820888 | None | None | N |
| P/T | 0.1438 | likely_benign | 0.1469 | benign | -0.557 | Destabilizing | 0.183 | N | 0.407 | neutral | N | 0.487228467 | None | None | N |
| P/V | 0.2318 | likely_benign | 0.2338 | benign | -0.367 | Destabilizing | 0.061 | N | 0.303 | neutral | None | None | None | None | N |
| P/W | 0.7045 | likely_pathogenic | 0.7448 | pathogenic | -0.754 | Destabilizing | 0.983 | D | 0.501 | neutral | None | None | None | None | N |
| P/Y | 0.516 | ambiguous | 0.5361 | ambiguous | -0.465 | Destabilizing | 0.836 | D | 0.589 | 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.