Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30774 | 92545;92546;92547 | chr2:178549306;178549305;178549304 | chr2:179414033;179414032;179414031 |
| N2AB | 29133 | 87622;87623;87624 | chr2:178549306;178549305;178549304 | chr2:179414033;179414032;179414031 |
| N2A | 28206 | 84841;84842;84843 | chr2:178549306;178549305;178549304 | chr2:179414033;179414032;179414031 |
| N2B | 21709 | 65350;65351;65352 | chr2:178549306;178549305;178549304 | chr2:179414033;179414032;179414031 |
| Novex-1 | 21834 | 65725;65726;65727 | chr2:178549306;178549305;178549304 | chr2:179414033;179414032;179414031 |
| Novex-2 | 21901 | 65926;65927;65928 | chr2:178549306;178549305;178549304 | chr2:179414033;179414032;179414031 |
| 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/A | rs1158503839  |
-0.95 | 0.543 | N | 0.261 | 0.185 | 0.218112801441 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| P/R | rs1399114641 |
-0.26 | 0.998 | N | 0.671 | 0.395 | 0.367992661779 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs1399114641 |
-0.26 | 0.998 | N | 0.671 | 0.395 | 0.367992661779 | gnomAD-4.0.0 | 1.59103E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | None | None | 0.978 | N | 0.562 | 0.274 | 0.286465849087 | gnomAD-4.0.0 | 6.8417E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99426E-07 | 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 | 0.0871 | likely_benign | 0.0825 | benign | -0.31 | Destabilizing | 0.543 | D | 0.261 | neutral | N | 0.490870913 | None | None | N |
| P/C | 0.4895 | ambiguous | 0.4794 | ambiguous | -0.652 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/D | 0.5394 | ambiguous | 0.4864 | ambiguous | 0.029 | Stabilizing | 0.998 | D | 0.626 | neutral | None | None | None | None | N |
| P/E | 0.3931 | ambiguous | 0.3431 | ambiguous | -0.083 | Destabilizing | 0.998 | D | 0.616 | neutral | None | None | None | None | N |
| P/F | 0.5223 | ambiguous | 0.4856 | ambiguous | -0.567 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| P/G | 0.3038 | likely_benign | 0.2839 | benign | -0.419 | Destabilizing | 0.992 | D | 0.485 | neutral | None | None | None | None | N |
| P/H | 0.2472 | likely_benign | 0.2158 | benign | -0.048 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| P/I | 0.3191 | likely_benign | 0.2889 | benign | -0.177 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | N |
| P/K | 0.3471 | ambiguous | 0.2936 | benign | -0.267 | Destabilizing | 0.998 | D | 0.613 | neutral | None | None | None | None | N |
| P/L | 0.1441 | likely_benign | 0.1312 | benign | -0.177 | Destabilizing | 0.997 | D | 0.638 | neutral | N | 0.459492 | None | None | N |
| P/M | 0.3141 | likely_benign | 0.2937 | benign | -0.349 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| P/N | 0.3168 | likely_benign | 0.2828 | benign | -0.049 | Destabilizing | 0.998 | D | 0.686 | prob.neutral | None | None | None | None | N |
| P/Q | 0.1874 | likely_benign | 0.1635 | benign | -0.253 | Destabilizing | 0.998 | D | 0.672 | neutral | N | 0.469202738 | None | None | N |
| P/R | 0.2587 | likely_benign | 0.2168 | benign | 0.157 | Stabilizing | 0.998 | D | 0.671 | neutral | N | 0.449640366 | None | None | N |
| P/S | 0.1468 | likely_benign | 0.1344 | benign | -0.424 | Destabilizing | 0.889 | D | 0.235 | neutral | N | 0.491465559 | None | None | N |
| P/T | 0.123 | likely_benign | 0.1111 | benign | -0.432 | Destabilizing | 0.978 | D | 0.562 | neutral | N | 0.449578864 | None | None | N |
| P/V | 0.2135 | likely_benign | 0.196 | benign | -0.188 | Destabilizing | 0.998 | D | 0.583 | neutral | None | None | None | None | N |
| P/W | 0.698 | likely_pathogenic | 0.6513 | pathogenic | -0.651 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/Y | 0.4788 | ambiguous | 0.44 | ambiguous | -0.342 | Destabilizing | 1.0 | D | 0.697 | prob.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.