Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20585 | 61978;61979;61980 | chr2:178589972;178589971;178589970 | chr2:179454699;179454698;179454697 |
| N2AB | 18944 | 57055;57056;57057 | chr2:178589972;178589971;178589970 | chr2:179454699;179454698;179454697 |
| N2A | 18017 | 54274;54275;54276 | chr2:178589972;178589971;178589970 | chr2:179454699;179454698;179454697 |
| N2B | 11520 | 34783;34784;34785 | chr2:178589972;178589971;178589970 | chr2:179454699;179454698;179454697 |
| Novex-1 | 11645 | 35158;35159;35160 | chr2:178589972;178589971;178589970 | chr2:179454699;179454698;179454697 |
| Novex-2 | 11712 | 35359;35360;35361 | chr2:178589972;178589971;178589970 | chr2:179454699;179454698;179454697 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/Y | rs574383177  |
-0.194 | 0.794 | N | 0.611 | 0.207 | 0.476205827853 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/Y | rs574383177 |
-0.194 | 0.794 | N | 0.611 | 0.207 | 0.476205827853 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| N/Y | rs574383177 |
-0.194 | 0.794 | N | 0.611 | 0.207 | 0.476205827853 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| N/Y | rs574383177 |
-0.194 | 0.794 | N | 0.611 | 0.207 | 0.476205827853 | gnomAD-4.0.0 | 1.85967E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.29453E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.2442 | likely_benign | 0.2255 | benign | -0.294 | Destabilizing | 0.001 | N | 0.371 | neutral | None | None | None | None | N |
| N/C | 0.2598 | likely_benign | 0.2389 | benign | 0.082 | Stabilizing | 0.94 | D | 0.627 | neutral | None | None | None | None | N |
| N/D | 0.306 | likely_benign | 0.2869 | benign | -1.655 | Destabilizing | 0.183 | N | 0.363 | neutral | N | 0.486483814 | None | None | N |
| N/E | 0.5874 | likely_pathogenic | 0.4933 | ambiguous | -1.568 | Destabilizing | 0.228 | N | 0.353 | neutral | None | None | None | None | N |
| N/F | 0.4534 | ambiguous | 0.4026 | ambiguous | -0.324 | Destabilizing | 0.836 | D | 0.636 | neutral | None | None | None | None | N |
| N/G | 0.3252 | likely_benign | 0.344 | ambiguous | -0.6 | Destabilizing | 0.061 | N | 0.288 | neutral | None | None | None | None | N |
| N/H | 0.1484 | likely_benign | 0.1419 | benign | -0.593 | Destabilizing | 0.921 | D | 0.529 | neutral | N | 0.464551103 | None | None | N |
| N/I | 0.2884 | likely_benign | 0.2216 | benign | 0.46 | Stabilizing | 0.213 | N | 0.615 | neutral | N | 0.498394318 | None | None | N |
| N/K | 0.5277 | ambiguous | 0.4316 | ambiguous | -0.183 | Destabilizing | 0.183 | N | 0.364 | neutral | N | 0.423837844 | None | None | N |
| N/L | 0.3132 | likely_benign | 0.2442 | benign | 0.46 | Stabilizing | 0.129 | N | 0.473 | neutral | None | None | None | None | N |
| N/M | 0.2986 | likely_benign | 0.2637 | benign | 0.979 | Stabilizing | 0.836 | D | 0.608 | neutral | None | None | None | None | N |
| N/P | 0.9858 | likely_pathogenic | 0.971 | pathogenic | 0.239 | Stabilizing | 0.593 | D | 0.559 | neutral | None | None | None | None | N |
| N/Q | 0.4099 | ambiguous | 0.3713 | ambiguous | -1.069 | Destabilizing | 0.593 | D | 0.501 | neutral | None | None | None | None | N |
| N/R | 0.5657 | likely_pathogenic | 0.4582 | ambiguous | -0.136 | Destabilizing | 0.418 | N | 0.439 | neutral | None | None | None | None | N |
| N/S | 0.0906 | likely_benign | 0.097 | benign | -0.765 | Destabilizing | 0.001 | N | 0.095 | neutral | N | 0.315259224 | None | None | N |
| N/T | 0.1155 | likely_benign | 0.1041 | benign | -0.524 | Destabilizing | 0.001 | N | 0.127 | neutral | N | 0.401979705 | None | None | N |
| N/V | 0.291 | likely_benign | 0.2318 | benign | 0.239 | Stabilizing | 0.129 | N | 0.495 | neutral | None | None | None | None | N |
| N/W | 0.8066 | likely_pathogenic | 0.7666 | pathogenic | -0.289 | Destabilizing | 0.983 | D | 0.635 | neutral | None | None | None | None | N |
| N/Y | 0.1577 | likely_benign | 0.1392 | benign | 0.084 | Stabilizing | 0.794 | D | 0.611 | neutral | N | 0.464031028 | 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.