Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26305 | 79138;79139;79140 | chr2:178567219;178567218;178567217 | chr2:179431946;179431945;179431944 |
| N2AB | 24664 | 74215;74216;74217 | chr2:178567219;178567218;178567217 | chr2:179431946;179431945;179431944 |
| N2A | 23737 | 71434;71435;71436 | chr2:178567219;178567218;178567217 | chr2:179431946;179431945;179431944 |
| N2B | 17240 | 51943;51944;51945 | chr2:178567219;178567218;178567217 | chr2:179431946;179431945;179431944 |
| Novex-1 | 17365 | 52318;52319;52320 | chr2:178567219;178567218;178567217 | chr2:179431946;179431945;179431944 |
| Novex-2 | 17432 | 52519;52520;52521 | chr2:178567219;178567218;178567217 | chr2:179431946;179431945;179431944 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs199646089  |
-0.921 | 0.78 | N | 0.579 | 0.215 | None | gnomAD-2.1.1 | 6.86E-05 | None | None | None | None | N | None | 7.86294E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs199646089 |
-0.921 | 0.78 | N | 0.579 | 0.215 | None | gnomAD-3.1.2 | 1.57795E-04 | None | None | None | None | N | None | 5.79206E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs199646089 |
-0.921 | 0.78 | N | 0.579 | 0.215 | None | gnomAD-4.0.0 | 2.9814E-05 | None | None | None | None | N | None | 6.42828E-04 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0904 | likely_benign | 0.0809 | benign | -0.684 | Destabilizing | None | N | 0.231 | neutral | N | 0.488948116 | None | None | N |
| S/C | 0.0766 | likely_benign | 0.0748 | benign | -0.528 | Destabilizing | 0.78 | D | 0.579 | neutral | N | 0.494298007 | None | None | N |
| S/D | 0.7084 | likely_pathogenic | 0.6553 | pathogenic | -0.459 | Destabilizing | 0.081 | N | 0.489 | neutral | None | None | None | None | N |
| S/E | 0.7591 | likely_pathogenic | 0.6903 | pathogenic | -0.471 | Destabilizing | 0.149 | N | 0.475 | neutral | None | None | None | None | N |
| S/F | 0.1086 | likely_benign | 0.1021 | benign | -0.95 | Destabilizing | 0.188 | N | 0.623 | neutral | N | 0.470763355 | None | None | N |
| S/G | 0.1416 | likely_benign | 0.1395 | benign | -0.914 | Destabilizing | 0.035 | N | 0.457 | neutral | None | None | None | None | N |
| S/H | 0.2916 | likely_benign | 0.2478 | benign | -1.458 | Destabilizing | 0.698 | D | 0.583 | neutral | None | None | None | None | N |
| S/I | 0.1073 | likely_benign | 0.0952 | benign | -0.181 | Destabilizing | 0.081 | N | 0.589 | neutral | None | None | None | None | N |
| S/K | 0.7807 | likely_pathogenic | 0.7181 | pathogenic | -0.684 | Destabilizing | 0.081 | N | 0.475 | neutral | None | None | None | None | N |
| S/L | 0.0699 | likely_benign | 0.0676 | benign | -0.181 | Destabilizing | 0.001 | N | 0.461 | neutral | None | None | None | None | N |
| S/M | 0.1015 | likely_benign | 0.092 | benign | 0.175 | Stabilizing | 0.38 | N | 0.597 | neutral | None | None | None | None | N |
| S/N | 0.1479 | likely_benign | 0.1345 | benign | -0.649 | Destabilizing | 0.001 | N | 0.399 | neutral | None | None | None | None | N |
| S/P | 0.8304 | likely_pathogenic | 0.8014 | pathogenic | -0.316 | Destabilizing | 0.484 | N | 0.582 | neutral | N | 0.489121099 | None | None | N |
| S/Q | 0.5102 | ambiguous | 0.4407 | ambiguous | -0.866 | Destabilizing | 0.38 | N | 0.537 | neutral | None | None | None | None | N |
| S/R | 0.7147 | likely_pathogenic | 0.6438 | pathogenic | -0.56 | Destabilizing | 0.38 | N | 0.589 | neutral | None | None | None | None | N |
| S/T | 0.0588 | likely_benign | 0.0566 | benign | -0.661 | Destabilizing | None | N | 0.231 | neutral | N | 0.372755663 | None | None | N |
| S/V | 0.1082 | likely_benign | 0.0937 | benign | -0.316 | Destabilizing | 0.081 | N | 0.553 | neutral | None | None | None | None | N |
| S/W | 0.2908 | likely_benign | 0.2622 | benign | -0.922 | Destabilizing | 0.935 | D | 0.699 | prob.neutral | None | None | None | None | N |
| S/Y | 0.134 | likely_benign | 0.1273 | benign | -0.646 | Destabilizing | 0.484 | N | 0.631 | neutral | N | 0.49637552 | 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.