Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25173 | 75742;75743;75744 | chr2:178570615;178570614;178570613 | chr2:179435342;179435341;179435340 |
| N2AB | 23532 | 70819;70820;70821 | chr2:178570615;178570614;178570613 | chr2:179435342;179435341;179435340 |
| N2A | 22605 | 68038;68039;68040 | chr2:178570615;178570614;178570613 | chr2:179435342;179435341;179435340 |
| N2B | 16108 | 48547;48548;48549 | chr2:178570615;178570614;178570613 | chr2:179435342;179435341;179435340 |
| Novex-1 | 16233 | 48922;48923;48924 | chr2:178570615;178570614;178570613 | chr2:179435342;179435341;179435340 |
| Novex-2 | 16300 | 49123;49124;49125 | chr2:178570615;178570614;178570613 | chr2:179435342;179435341;179435340 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1707836839  |
None | None | N | 0.151 | 0.052 | 0.0551355673512 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85915E-06 | 0 | 0 |
| D/H | rs980015868 |
None | 0.773 | N | 0.383 | 0.443 | 0.193865811164 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| D/H | rs980015868 |
None | 0.773 | N | 0.383 | 0.443 | 0.193865811164 | gnomAD-4.0.0 | 7.43784E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01725E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2911 | likely_benign | 0.2822 | benign | -0.392 | Destabilizing | 0.193 | N | 0.353 | neutral | N | 0.456883883 | None | None | N |
| D/C | 0.7611 | likely_pathogenic | 0.7747 | pathogenic | 0.112 | Stabilizing | 0.981 | D | 0.542 | neutral | None | None | None | None | N |
| D/E | 0.1475 | likely_benign | 0.1219 | benign | -0.288 | Destabilizing | None | N | 0.151 | neutral | N | 0.44208717 | None | None | N |
| D/F | 0.6919 | likely_pathogenic | 0.7035 | pathogenic | -0.436 | Destabilizing | 0.932 | D | 0.474 | neutral | None | None | None | None | N |
| D/G | 0.2307 | likely_benign | 0.2177 | benign | -0.58 | Destabilizing | 0.324 | N | 0.313 | neutral | N | 0.5097736 | None | None | N |
| D/H | 0.4701 | ambiguous | 0.485 | ambiguous | -0.406 | Destabilizing | 0.773 | D | 0.383 | neutral | N | 0.474596518 | None | None | N |
| D/I | 0.6238 | likely_pathogenic | 0.6233 | pathogenic | 0.056 | Stabilizing | 0.818 | D | 0.481 | neutral | None | None | None | None | N |
| D/K | 0.5711 | likely_pathogenic | 0.5696 | pathogenic | 0.285 | Stabilizing | 0.241 | N | 0.301 | neutral | None | None | None | None | N |
| D/L | 0.5455 | ambiguous | 0.5382 | ambiguous | 0.056 | Stabilizing | 0.69 | D | 0.431 | neutral | None | None | None | None | N |
| D/M | 0.7136 | likely_pathogenic | 0.7013 | pathogenic | 0.342 | Stabilizing | 0.981 | D | 0.469 | neutral | None | None | None | None | N |
| D/N | 0.1638 | likely_benign | 0.1591 | benign | 0.033 | Stabilizing | 0.324 | N | 0.355 | neutral | N | 0.444892615 | None | None | N |
| D/P | 0.923 | likely_pathogenic | 0.9327 | pathogenic | -0.072 | Destabilizing | 0.818 | D | 0.348 | neutral | None | None | None | None | N |
| D/Q | 0.4782 | ambiguous | 0.4492 | ambiguous | 0.055 | Stabilizing | 0.241 | N | 0.303 | neutral | None | None | None | None | N |
| D/R | 0.6493 | likely_pathogenic | 0.6605 | pathogenic | 0.35 | Stabilizing | 0.69 | D | 0.411 | neutral | None | None | None | None | N |
| D/S | 0.2413 | likely_benign | 0.2281 | benign | -0.082 | Destabilizing | 0.241 | N | 0.316 | neutral | None | None | None | None | N |
| D/T | 0.441 | ambiguous | 0.4295 | ambiguous | 0.064 | Stabilizing | 0.388 | N | 0.36 | neutral | None | None | None | None | N |
| D/V | 0.3734 | ambiguous | 0.3858 | ambiguous | -0.072 | Destabilizing | 0.627 | D | 0.43 | neutral | N | 0.490245237 | None | None | N |
| D/W | 0.9031 | likely_pathogenic | 0.9157 | pathogenic | -0.321 | Destabilizing | 0.981 | D | 0.6 | neutral | None | None | None | None | N |
| D/Y | 0.2427 | likely_benign | 0.2782 | benign | -0.211 | Destabilizing | 0.912 | D | 0.475 | neutral | N | 0.467114553 | 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.