Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23877 | 71854;71855;71856 | chr2:178574503;178574502;178574501 | chr2:179439230;179439229;179439228 |
| N2AB | 22236 | 66931;66932;66933 | chr2:178574503;178574502;178574501 | chr2:179439230;179439229;179439228 |
| N2A | 21309 | 64150;64151;64152 | chr2:178574503;178574502;178574501 | chr2:179439230;179439229;179439228 |
| N2B | 14812 | 44659;44660;44661 | chr2:178574503;178574502;178574501 | chr2:179439230;179439229;179439228 |
| Novex-1 | 14937 | 45034;45035;45036 | chr2:178574503;178574502;178574501 | chr2:179439230;179439229;179439228 |
| Novex-2 | 15004 | 45235;45236;45237 | chr2:178574503;178574502;178574501 | chr2:179439230;179439229;179439228 |
| 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/N | rs1239475601  |
-0.597 | 0.026 | N | 0.341 | 0.147 | 0.176091768786 | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 2.29621E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs1239475601 |
-0.597 | 0.026 | N | 0.341 | 0.147 | 0.176091768786 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs1239475601 |
-0.597 | 0.026 | N | 0.341 | 0.147 | 0.176091768786 | gnomAD-4.0.0 | 5.12552E-06 | None | None | None | None | N | None | 5.07357E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.39389E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2235 | likely_benign | 0.2193 | benign | -0.702 | Destabilizing | 0.825 | D | 0.481 | neutral | None | None | None | None | N |
| S/C | 0.221 | likely_benign | 0.1998 | benign | -0.371 | Destabilizing | 0.999 | D | 0.643 | neutral | N | 0.470727356 | None | None | N |
| S/D | 0.8661 | likely_pathogenic | 0.8459 | pathogenic | -0.23 | Destabilizing | 0.851 | D | 0.533 | neutral | None | None | None | None | N |
| S/E | 0.9397 | likely_pathogenic | 0.9386 | pathogenic | -0.18 | Destabilizing | 0.919 | D | 0.546 | neutral | None | None | None | None | N |
| S/F | 0.8656 | likely_pathogenic | 0.8607 | pathogenic | -0.74 | Destabilizing | 0.996 | D | 0.682 | prob.neutral | None | None | None | None | N |
| S/G | 0.1662 | likely_benign | 0.1503 | benign | -1.011 | Destabilizing | 0.811 | D | 0.485 | neutral | N | 0.477579116 | None | None | N |
| S/H | 0.8376 | likely_pathogenic | 0.8118 | pathogenic | -1.474 | Destabilizing | 0.997 | D | 0.651 | neutral | None | None | None | None | N |
| S/I | 0.6749 | likely_pathogenic | 0.668 | pathogenic | 0.027 | Stabilizing | 0.968 | D | 0.661 | neutral | N | 0.487139961 | None | None | N |
| S/K | 0.982 | likely_pathogenic | 0.9794 | pathogenic | -0.607 | Destabilizing | 0.919 | D | 0.543 | neutral | None | None | None | None | N |
| S/L | 0.4357 | ambiguous | 0.4199 | ambiguous | 0.027 | Stabilizing | 0.919 | D | 0.573 | neutral | None | None | None | None | N |
| S/M | 0.6309 | likely_pathogenic | 0.6097 | pathogenic | 0.183 | Stabilizing | 0.999 | D | 0.647 | neutral | None | None | None | None | N |
| S/N | 0.2646 | likely_benign | 0.2456 | benign | -0.681 | Destabilizing | 0.026 | N | 0.341 | neutral | N | 0.349649517 | None | None | N |
| S/P | 0.8638 | likely_pathogenic | 0.8514 | pathogenic | -0.18 | Destabilizing | 0.996 | D | 0.651 | neutral | None | None | None | None | N |
| S/Q | 0.9094 | likely_pathogenic | 0.9045 | pathogenic | -0.674 | Destabilizing | 0.988 | D | 0.635 | neutral | None | None | None | None | N |
| S/R | 0.97 | likely_pathogenic | 0.9653 | pathogenic | -0.679 | Destabilizing | 0.968 | D | 0.637 | neutral | N | 0.481579426 | None | None | N |
| S/T | 0.1394 | likely_benign | 0.1366 | benign | -0.617 | Destabilizing | 0.103 | N | 0.341 | neutral | N | 0.432630686 | None | None | N |
| S/V | 0.5984 | likely_pathogenic | 0.5851 | pathogenic | -0.18 | Destabilizing | 0.976 | D | 0.607 | neutral | None | None | None | None | N |
| S/W | 0.8958 | likely_pathogenic | 0.8875 | pathogenic | -0.8 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | N |
| S/Y | 0.7572 | likely_pathogenic | 0.7533 | pathogenic | -0.495 | Destabilizing | 0.996 | D | 0.677 | 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.