Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21057 | 63394;63395;63396 | chr2:178588556;178588555;178588554 | chr2:179453283;179453282;179453281 |
| N2AB | 19416 | 58471;58472;58473 | chr2:178588556;178588555;178588554 | chr2:179453283;179453282;179453281 |
| N2A | 18489 | 55690;55691;55692 | chr2:178588556;178588555;178588554 | chr2:179453283;179453282;179453281 |
| N2B | 11992 | 36199;36200;36201 | chr2:178588556;178588555;178588554 | chr2:179453283;179453282;179453281 |
| Novex-1 | 12117 | 36574;36575;36576 | chr2:178588556;178588555;178588554 | chr2:179453283;179453282;179453281 |
| Novex-2 | 12184 | 36775;36776;36777 | chr2:178588556;178588555;178588554 | chr2:179453283;179453282;179453281 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs2049556477  |
None | 0.278 | N | 0.43 | 0.101 | 0.300784259202 | 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 |
| V/L | rs2049556477 |
None | 0.278 | N | 0.43 | 0.101 | 0.300784259202 | gnomAD-4.0.0 | 1.30692E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.75032E-06 | 0 | 0 |
| V/M | rs2049556477 |
None | 0.868 | N | 0.406 | 0.105 | 0.380394304726 | 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 |
| V/M | rs2049556477 |
None | 0.868 | N | 0.406 | 0.105 | 0.380394304726 | gnomAD-4.0.0 | 2.61384E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62548E-06 | 1.3438E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1358 | likely_benign | 0.1196 | benign | -1.343 | Destabilizing | 0.01 | N | 0.085 | neutral | N | 0.480363131 | None | None | N |
| V/C | 0.61 | likely_pathogenic | 0.5486 | ambiguous | -0.818 | Destabilizing | 0.995 | D | 0.356 | neutral | None | None | None | None | N |
| V/D | 0.4973 | ambiguous | 0.3996 | ambiguous | -1.227 | Destabilizing | 0.946 | D | 0.562 | neutral | None | None | None | None | N |
| V/E | 0.3542 | ambiguous | 0.2587 | benign | -1.273 | Destabilizing | 0.93 | D | 0.508 | neutral | N | 0.463105522 | None | None | N |
| V/F | 0.1593 | likely_benign | 0.137 | benign | -1.164 | Destabilizing | 0.897 | D | 0.438 | neutral | None | None | None | None | N |
| V/G | 0.2633 | likely_benign | 0.2256 | benign | -1.612 | Destabilizing | 0.651 | D | 0.521 | neutral | N | 0.471200519 | None | None | N |
| V/H | 0.4937 | ambiguous | 0.4231 | ambiguous | -1.109 | Destabilizing | 0.995 | D | 0.539 | neutral | None | None | None | None | N |
| V/I | 0.0736 | likely_benign | 0.0675 | benign | -0.723 | Destabilizing | 0.003 | N | 0.115 | neutral | None | None | None | None | N |
| V/K | 0.2528 | likely_benign | 0.203 | benign | -1.139 | Destabilizing | 0.897 | D | 0.519 | neutral | None | None | None | None | N |
| V/L | 0.1424 | likely_benign | 0.1178 | benign | -0.723 | Destabilizing | 0.278 | N | 0.43 | neutral | N | 0.416831727 | None | None | N |
| V/M | 0.1177 | likely_benign | 0.1022 | benign | -0.466 | Destabilizing | 0.868 | D | 0.406 | neutral | N | 0.453504603 | None | None | N |
| V/N | 0.2985 | likely_benign | 0.2412 | benign | -0.85 | Destabilizing | 0.946 | D | 0.599 | neutral | None | None | None | None | N |
| V/P | 0.354 | ambiguous | 0.3406 | ambiguous | -0.894 | Destabilizing | 0.946 | D | 0.545 | neutral | None | None | None | None | N |
| V/Q | 0.2891 | likely_benign | 0.2324 | benign | -1.091 | Destabilizing | 0.982 | D | 0.527 | neutral | None | None | None | None | N |
| V/R | 0.2272 | likely_benign | 0.1835 | benign | -0.515 | Destabilizing | 0.946 | D | 0.613 | neutral | None | None | None | None | N |
| V/S | 0.1996 | likely_benign | 0.1712 | benign | -1.306 | Destabilizing | 0.553 | D | 0.502 | neutral | None | None | None | None | N |
| V/T | 0.1239 | likely_benign | 0.1108 | benign | -1.251 | Destabilizing | 0.032 | N | 0.187 | neutral | None | None | None | None | N |
| V/W | 0.7004 | likely_pathogenic | 0.6448 | pathogenic | -1.3 | Destabilizing | 0.995 | D | 0.665 | prob.neutral | None | None | None | None | N |
| V/Y | 0.4775 | ambiguous | 0.3968 | ambiguous | -1.035 | Destabilizing | 0.982 | D | 0.435 | 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.