Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16460 | 49603;49604;49605 | chr2:178613905;178613904;178613903 | chr2:179478632;179478631;179478630 |
| N2AB | 14819 | 44680;44681;44682 | chr2:178613905;178613904;178613903 | chr2:179478632;179478631;179478630 |
| N2A | 13892 | 41899;41900;41901 | chr2:178613905;178613904;178613903 | chr2:179478632;179478631;179478630 |
| N2B | 7395 | 22408;22409;22410 | chr2:178613905;178613904;178613903 | chr2:179478632;179478631;179478630 |
| Novex-1 | 7520 | 22783;22784;22785 | chr2:178613905;178613904;178613903 | chr2:179478632;179478631;179478630 |
| Novex-2 | 7587 | 22984;22985;22986 | chr2:178613905;178613904;178613903 | chr2:179478632;179478631;179478630 |
| 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 | rs397517596  |
-0.127 | 0.99 | D | 0.43 | 0.327 | 0.41337360676 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.59E-05 | 0 |
| S/C | rs397517596 |
-0.127 | 0.99 | D | 0.43 | 0.327 | 0.41337360676 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/C | rs397517596 |
-0.127 | 0.99 | D | 0.43 | 0.327 | 0.41337360676 | gnomAD-4.0.0 | 2.36007E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.05604E-05 | 0 | 3.2113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0916 | likely_benign | 0.0918 | benign | -0.614 | Destabilizing | 0.201 | N | 0.395 | neutral | N | 0.47655632 | None | None | N |
| S/C | 0.1542 | likely_benign | 0.1439 | benign | -0.443 | Destabilizing | 0.99 | D | 0.43 | neutral | D | 0.536747237 | None | None | N |
| S/D | 0.7166 | likely_pathogenic | 0.6958 | pathogenic | -0.026 | Destabilizing | 0.617 | D | 0.399 | neutral | None | None | None | None | N |
| S/E | 0.6777 | likely_pathogenic | 0.6715 | pathogenic | -0.089 | Destabilizing | 0.617 | D | 0.413 | neutral | None | None | None | None | N |
| S/F | 0.3634 | ambiguous | 0.3348 | benign | -1.089 | Destabilizing | 0.81 | D | 0.546 | neutral | D | 0.557510813 | None | None | N |
| S/G | 0.152 | likely_benign | 0.1459 | benign | -0.774 | Destabilizing | 0.617 | D | 0.383 | neutral | None | None | None | None | N |
| S/H | 0.5232 | ambiguous | 0.4973 | ambiguous | -1.302 | Destabilizing | 0.992 | D | 0.429 | neutral | None | None | None | None | N |
| S/I | 0.266 | likely_benign | 0.2588 | benign | -0.312 | Destabilizing | 0.005 | N | 0.294 | neutral | None | None | None | None | N |
| S/K | 0.7628 | likely_pathogenic | 0.7523 | pathogenic | -0.587 | Destabilizing | 0.617 | D | 0.409 | neutral | None | None | None | None | N |
| S/L | 0.1527 | likely_benign | 0.1484 | benign | -0.312 | Destabilizing | 0.25 | N | 0.426 | neutral | None | None | None | None | N |
| S/M | 0.2344 | likely_benign | 0.229 | benign | 0.029 | Stabilizing | 0.85 | D | 0.449 | neutral | None | None | None | None | N |
| S/N | 0.2782 | likely_benign | 0.2735 | benign | -0.413 | Destabilizing | 0.617 | D | 0.452 | neutral | None | None | None | None | N |
| S/P | 0.9706 | likely_pathogenic | 0.9661 | pathogenic | -0.382 | Destabilizing | 0.896 | D | 0.471 | neutral | D | 0.556635951 | None | None | N |
| S/Q | 0.5681 | likely_pathogenic | 0.5604 | ambiguous | -0.668 | Destabilizing | 0.92 | D | 0.452 | neutral | None | None | None | None | N |
| S/R | 0.7319 | likely_pathogenic | 0.7083 | pathogenic | -0.389 | Destabilizing | 0.85 | D | 0.469 | neutral | None | None | None | None | N |
| S/T | 0.0828 | likely_benign | 0.0827 | benign | -0.506 | Destabilizing | 0.002 | N | 0.108 | neutral | N | 0.459805548 | None | None | N |
| S/V | 0.2164 | likely_benign | 0.2114 | benign | -0.382 | Destabilizing | 0.005 | N | 0.327 | neutral | None | None | None | None | N |
| S/W | 0.6161 | likely_pathogenic | 0.5764 | pathogenic | -1.036 | Destabilizing | 0.992 | D | 0.635 | neutral | None | None | None | None | N |
| S/Y | 0.3784 | ambiguous | 0.3478 | ambiguous | -0.775 | Destabilizing | 0.896 | D | 0.527 | neutral | D | 0.556635951 | 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.