Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3954 | 12085;12086;12087 | chr2:178741373;178741372;178741371 | chr2:179606100;179606099;179606098 |
| N2AB | 3637 | 11134;11135;11136 | chr2:178741373;178741372;178741371 | chr2:179606100;179606099;179606098 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3591 | 10996;10997;10998 | chr2:178741373;178741372;178741371 | chr2:179606100;179606099;179606098 |
| Novex-1 | 3716 | 11371;11372;11373 | chr2:178741373;178741372;178741371 | chr2:179606100;179606099;179606098 |
| Novex-2 | 3783 | 11572;11573;11574 | chr2:178741373;178741372;178741371 | chr2:179606100;179606099;179606098 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1287785786  |
-0.634 | 0.27 | N | 0.343 | 0.216 | 0.43912465853 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| P/L | rs1287785786 |
-0.634 | 0.27 | N | 0.343 | 0.216 | 0.43912465853 | gnomAD-4.0.0 | 3.42089E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49718E-06 | 0 | 0 |
| P/S | rs757223770 |
-0.99 | 0.01 | N | 0.135 | 0.098 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| P/S | rs757223770 |
-0.99 | 0.01 | N | 0.135 | 0.098 | None | gnomAD-4.0.0 | 1.59107E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85789E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2027 | likely_benign | 0.1981 | benign | -1.243 | Destabilizing | 0.01 | N | 0.118 | neutral | N | 0.450421647 | None | None | I |
| P/C | 0.8485 | likely_pathogenic | 0.8512 | pathogenic | -0.755 | Destabilizing | 0.981 | D | 0.351 | neutral | None | None | None | None | I |
| P/D | 0.9045 | likely_pathogenic | 0.8974 | pathogenic | -1.151 | Destabilizing | 0.329 | N | 0.34 | neutral | None | None | None | None | I |
| P/E | 0.7493 | likely_pathogenic | 0.7384 | pathogenic | -1.202 | Destabilizing | 0.004 | N | 0.111 | neutral | None | None | None | None | I |
| P/F | 0.8737 | likely_pathogenic | 0.8775 | pathogenic | -1.102 | Destabilizing | 0.944 | D | 0.381 | neutral | None | None | None | None | I |
| P/G | 0.7625 | likely_pathogenic | 0.7478 | pathogenic | -1.495 | Destabilizing | 0.329 | N | 0.327 | neutral | None | None | None | None | I |
| P/H | 0.5869 | likely_pathogenic | 0.5985 | pathogenic | -1.013 | Destabilizing | 0.975 | D | 0.355 | neutral | N | 0.509029802 | None | None | I |
| P/I | 0.7476 | likely_pathogenic | 0.7572 | pathogenic | -0.675 | Destabilizing | 0.704 | D | 0.416 | neutral | None | None | None | None | I |
| P/K | 0.7715 | likely_pathogenic | 0.7865 | pathogenic | -1.139 | Destabilizing | 0.329 | N | 0.354 | neutral | None | None | None | None | I |
| P/L | 0.3199 | likely_benign | 0.3464 | ambiguous | -0.675 | Destabilizing | 0.27 | N | 0.343 | neutral | N | 0.467502048 | None | None | I |
| P/M | 0.732 | likely_pathogenic | 0.7368 | pathogenic | -0.459 | Destabilizing | 0.981 | D | 0.351 | neutral | None | None | None | None | I |
| P/N | 0.8449 | likely_pathogenic | 0.8386 | pathogenic | -0.827 | Destabilizing | 0.704 | D | 0.328 | neutral | None | None | None | None | I |
| P/Q | 0.5241 | ambiguous | 0.5278 | ambiguous | -1.056 | Destabilizing | 0.704 | D | 0.311 | neutral | None | None | None | None | I |
| P/R | 0.538 | ambiguous | 0.5636 | ambiguous | -0.517 | Destabilizing | 0.642 | D | 0.353 | neutral | N | 0.449769997 | None | None | I |
| P/S | 0.4098 | ambiguous | 0.4066 | ambiguous | -1.244 | Destabilizing | 0.01 | N | 0.135 | neutral | N | 0.443190445 | None | None | I |
| P/T | 0.3621 | ambiguous | 0.3613 | ambiguous | -1.195 | Destabilizing | 0.003 | N | 0.112 | neutral | N | 0.436518385 | None | None | I |
| P/V | 0.5853 | likely_pathogenic | 0.5871 | pathogenic | -0.829 | Destabilizing | 0.329 | N | 0.32 | neutral | None | None | None | None | I |
| P/W | 0.9329 | likely_pathogenic | 0.9299 | pathogenic | -1.241 | Destabilizing | 0.995 | D | 0.379 | neutral | None | None | None | None | I |
| P/Y | 0.8395 | likely_pathogenic | 0.845 | pathogenic | -0.981 | Destabilizing | 0.981 | D | 0.381 | neutral | None | None | None | None | I |
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.