Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20974 | 63145;63146;63147 | chr2:178588805;178588804;178588803 | chr2:179453532;179453531;179453530 |
| N2AB | 19333 | 58222;58223;58224 | chr2:178588805;178588804;178588803 | chr2:179453532;179453531;179453530 |
| N2A | 18406 | 55441;55442;55443 | chr2:178588805;178588804;178588803 | chr2:179453532;179453531;179453530 |
| N2B | 11909 | 35950;35951;35952 | chr2:178588805;178588804;178588803 | chr2:179453532;179453531;179453530 |
| Novex-1 | 12034 | 36325;36326;36327 | chr2:178588805;178588804;178588803 | chr2:179453532;179453531;179453530 |
| Novex-2 | 12101 | 36526;36527;36528 | chr2:178588805;178588804;178588803 | chr2:179453532;179453531;179453530 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs370100134  |
0.266 | 0.977 | N | 0.54 | 0.244 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| K/E | rs370100134 |
0.266 | 0.977 | N | 0.54 | 0.244 | None | 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 |
| K/E | rs370100134 |
0.266 | 0.977 | N | 0.54 | 0.244 | None | gnomAD-4.0.0 | 8.67813E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10209E-05 | 0 | 1.60149E-05 |
| K/N | None | None | 0.993 | N | 0.673 | 0.162 | 0.206339911435 | gnomAD-4.0.0 | 1.59222E-06 | None | None | None | None | N | None | 0 | 2.28822E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.5411 | ambiguous | 0.357 | ambiguous | -0.023 | Destabilizing | 0.983 | D | 0.565 | neutral | None | None | None | None | N |
| K/C | 0.8127 | likely_pathogenic | 0.6792 | pathogenic | -0.254 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| K/D | 0.8104 | likely_pathogenic | 0.6451 | pathogenic | 0.209 | Stabilizing | 0.998 | D | 0.703 | prob.neutral | None | None | None | None | N |
| K/E | 0.5025 | ambiguous | 0.3111 | benign | 0.228 | Stabilizing | 0.977 | D | 0.54 | neutral | N | 0.445442481 | None | None | N |
| K/F | 0.9081 | likely_pathogenic | 0.8255 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| K/G | 0.6612 | likely_pathogenic | 0.4686 | ambiguous | -0.245 | Destabilizing | 0.998 | D | 0.535 | neutral | None | None | None | None | N |
| K/H | 0.4388 | ambiguous | 0.3131 | benign | -0.508 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| K/I | 0.7418 | likely_pathogenic | 0.5708 | pathogenic | 0.487 | Stabilizing | 0.997 | D | 0.717 | prob.delet. | N | 0.512304978 | None | None | N |
| K/L | 0.6417 | likely_pathogenic | 0.477 | ambiguous | 0.487 | Stabilizing | 0.995 | D | 0.535 | neutral | None | None | None | None | N |
| K/M | 0.4719 | ambiguous | 0.3228 | benign | 0.271 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| K/N | 0.6986 | likely_pathogenic | 0.5217 | ambiguous | 0.2 | Stabilizing | 0.993 | D | 0.673 | neutral | N | 0.429531666 | None | None | N |
| K/P | 0.9682 | likely_pathogenic | 0.933 | pathogenic | 0.346 | Stabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| K/Q | 0.2802 | likely_benign | 0.1807 | benign | 0.03 | Stabilizing | 0.993 | D | 0.668 | neutral | N | 0.487561249 | None | None | N |
| K/R | 0.0817 | likely_benign | 0.0769 | benign | -0.042 | Destabilizing | 0.235 | N | 0.25 | neutral | N | 0.480923278 | None | None | N |
| K/S | 0.6705 | likely_pathogenic | 0.4709 | ambiguous | -0.348 | Destabilizing | 0.983 | D | 0.608 | neutral | None | None | None | None | N |
| K/T | 0.4509 | ambiguous | 0.2643 | benign | -0.169 | Destabilizing | 0.997 | D | 0.635 | neutral | N | 0.493583144 | None | None | N |
| K/V | 0.5919 | likely_pathogenic | 0.434 | ambiguous | 0.346 | Stabilizing | 0.998 | D | 0.67 | neutral | None | None | None | None | N |
| K/W | 0.8602 | likely_pathogenic | 0.7551 | pathogenic | -0.143 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| K/Y | 0.7928 | likely_pathogenic | 0.654 | pathogenic | 0.209 | Stabilizing | 0.999 | D | 0.691 | 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.