Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26131 | 78616;78617;78618 | chr2:178567741;178567740;178567739 | chr2:179432468;179432467;179432466 |
| N2AB | 24490 | 73693;73694;73695 | chr2:178567741;178567740;178567739 | chr2:179432468;179432467;179432466 |
| N2A | 23563 | 70912;70913;70914 | chr2:178567741;178567740;178567739 | chr2:179432468;179432467;179432466 |
| N2B | 17066 | 51421;51422;51423 | chr2:178567741;178567740;178567739 | chr2:179432468;179432467;179432466 |
| Novex-1 | 17191 | 51796;51797;51798 | chr2:178567741;178567740;178567739 | chr2:179432468;179432467;179432466 |
| Novex-2 | 17258 | 51997;51998;51999 | chr2:178567741;178567740;178567739 | chr2:179432468;179432467;179432466 |
| 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/L | None | None | 1.0 | N | 0.678 | 0.518 | 0.45553875121 | gnomAD-4.0.0 | 1.59355E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43328E-05 | 0 |
| P/S | rs764676279  |
-0.334 | 1.0 | N | 0.577 | 0.413 | 0.231231049324 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| P/S | rs764676279 |
-0.334 | 1.0 | N | 0.577 | 0.413 | 0.231231049324 | gnomAD-4.0.0 | 6.37448E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14553E-05 | 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 | 0.3567 | ambiguous | 0.3364 | benign | -0.367 | Destabilizing | 1.0 | D | 0.529 | neutral | N | 0.502247408 | None | None | N |
| P/C | 0.9087 | likely_pathogenic | 0.9037 | pathogenic | -0.717 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | None | None | None | None | N |
| P/D | 0.847 | likely_pathogenic | 0.8486 | pathogenic | -0.394 | Destabilizing | 1.0 | D | 0.555 | neutral | None | None | None | None | N |
| P/E | 0.7079 | likely_pathogenic | 0.7049 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.563 | neutral | None | None | None | None | N |
| P/F | 0.9447 | likely_pathogenic | 0.9385 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| P/G | 0.6531 | likely_pathogenic | 0.6612 | pathogenic | -0.45 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| P/H | 0.7199 | likely_pathogenic | 0.7151 | pathogenic | -0.01 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.469362143 | None | None | N |
| P/I | 0.8275 | likely_pathogenic | 0.8137 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| P/K | 0.772 | likely_pathogenic | 0.7626 | pathogenic | -0.407 | Destabilizing | 1.0 | D | 0.558 | neutral | None | None | None | None | N |
| P/L | 0.4983 | ambiguous | 0.4874 | ambiguous | -0.297 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | N | 0.465096182 | None | None | N |
| P/M | 0.79 | likely_pathogenic | 0.7852 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| P/N | 0.8166 | likely_pathogenic | 0.8308 | pathogenic | -0.182 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | N |
| P/Q | 0.6234 | likely_pathogenic | 0.6324 | pathogenic | -0.426 | Destabilizing | 1.0 | D | 0.585 | neutral | None | None | None | None | N |
| P/R | 0.6602 | likely_pathogenic | 0.648 | pathogenic | 0.101 | Stabilizing | 1.0 | D | 0.639 | neutral | N | 0.491646412 | None | None | N |
| P/S | 0.5629 | ambiguous | 0.5588 | ambiguous | -0.488 | Destabilizing | 1.0 | D | 0.577 | neutral | N | 0.487045882 | None | None | N |
| P/T | 0.4234 | ambiguous | 0.4175 | ambiguous | -0.516 | Destabilizing | 1.0 | D | 0.567 | neutral | N | 0.504940996 | None | None | N |
| P/V | 0.7043 | likely_pathogenic | 0.6804 | pathogenic | -0.29 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| P/W | 0.9671 | likely_pathogenic | 0.9609 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/Y | 0.9211 | likely_pathogenic | 0.913 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.671 | 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.