Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35612 | 107059;107060;107061 | chr2:178528917;178528916;178528915 | chr2:179393644;179393643;179393642 |
| N2AB | 33971 | 102136;102137;102138 | chr2:178528917;178528916;178528915 | chr2:179393644;179393643;179393642 |
| N2A | 33044 | 99355;99356;99357 | chr2:178528917;178528916;178528915 | chr2:179393644;179393643;179393642 |
| N2B | 26547 | 79864;79865;79866 | chr2:178528917;178528916;178528915 | chr2:179393644;179393643;179393642 |
| Novex-1 | 26672 | 80239;80240;80241 | chr2:178528917;178528916;178528915 | chr2:179393644;179393643;179393642 |
| Novex-2 | 26739 | 80440;80441;80442 | chr2:178528917;178528916;178528915 | chr2:179393644;179393643;179393642 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/S | rs762372340  |
-2.942 | None | N | 0.197 | 0.129 | 0.300784259202 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/S | rs762372340 |
-2.942 | None | N | 0.197 | 0.129 | 0.300784259202 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/S | rs762372340 |
-2.942 | None | N | 0.197 | 0.129 | 0.300784259202 | gnomAD-4.0.0 | 3.71768E-06 | None | None | None | None | N | None | 8.00683E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.2309 | likely_benign | 0.3104 | benign | -0.651 | Destabilizing | 0.007 | N | 0.307 | neutral | None | None | None | None | N |
| F/C | 0.2908 | likely_benign | 0.3279 | benign | -0.199 | Destabilizing | 0.295 | N | 0.485 | neutral | N | 0.449422227 | None | None | N |
| F/D | 0.4512 | ambiguous | 0.5808 | pathogenic | 0.993 | Stabilizing | 0.038 | N | 0.495 | neutral | None | None | None | None | N |
| F/E | 0.5604 | ambiguous | 0.6703 | pathogenic | 0.961 | Stabilizing | 0.016 | N | 0.463 | neutral | None | None | None | None | N |
| F/G | 0.476 | ambiguous | 0.5648 | pathogenic | -0.817 | Destabilizing | 0.016 | N | 0.398 | neutral | None | None | None | None | N |
| F/H | 0.4094 | ambiguous | 0.4921 | ambiguous | 0.325 | Stabilizing | 0.214 | N | 0.452 | neutral | None | None | None | None | N |
| F/I | 0.1232 | likely_benign | 0.1446 | benign | -0.249 | Destabilizing | 0.012 | N | 0.375 | neutral | N | 0.447515286 | None | None | N |
| F/K | 0.5655 | likely_pathogenic | 0.6622 | pathogenic | 0.129 | Stabilizing | 0.016 | N | 0.449 | neutral | None | None | None | None | N |
| F/L | 0.5909 | likely_pathogenic | 0.6457 | pathogenic | -0.249 | Destabilizing | None | N | 0.128 | neutral | N | 0.429622958 | None | None | N |
| F/M | 0.3621 | ambiguous | 0.4073 | ambiguous | -0.228 | Destabilizing | 0.12 | N | 0.444 | neutral | None | None | None | None | N |
| F/N | 0.3065 | likely_benign | 0.41 | ambiguous | 0.199 | Stabilizing | 0.038 | N | 0.491 | neutral | None | None | None | None | N |
| F/P | 0.7203 | likely_pathogenic | 0.7836 | pathogenic | -0.363 | Destabilizing | 0.072 | N | 0.541 | neutral | None | None | None | None | N |
| F/Q | 0.5092 | ambiguous | 0.6076 | pathogenic | 0.173 | Stabilizing | 0.072 | N | 0.546 | neutral | None | None | None | None | N |
| F/R | 0.4697 | ambiguous | 0.5593 | ambiguous | 0.466 | Stabilizing | 0.072 | N | 0.531 | neutral | None | None | None | None | N |
| F/S | 0.1473 | likely_benign | 0.2143 | benign | -0.455 | Destabilizing | None | N | 0.197 | neutral | N | 0.404668586 | None | None | N |
| F/T | 0.2104 | likely_benign | 0.2998 | benign | -0.393 | Destabilizing | None | N | 0.219 | neutral | None | None | None | None | N |
| F/V | 0.1225 | likely_benign | 0.1432 | benign | -0.363 | Destabilizing | 0.005 | N | 0.347 | neutral | N | 0.447862002 | None | None | N |
| F/W | 0.4619 | ambiguous | 0.4894 | ambiguous | -0.215 | Destabilizing | 0.356 | N | 0.459 | neutral | None | None | None | None | N |
| F/Y | 0.1422 | likely_benign | 0.1578 | benign | -0.14 | Destabilizing | None | N | 0.165 | neutral | N | 0.449248869 | 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.