Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22035 | 66328;66329;66330 | chr2:178582353;178582352;178582351 | chr2:179447080;179447079;179447078 |
| N2AB | 20394 | 61405;61406;61407 | chr2:178582353;178582352;178582351 | chr2:179447080;179447079;179447078 |
| N2A | 19467 | 58624;58625;58626 | chr2:178582353;178582352;178582351 | chr2:179447080;179447079;179447078 |
| N2B | 12970 | 39133;39134;39135 | chr2:178582353;178582352;178582351 | chr2:179447080;179447079;179447078 |
| Novex-1 | 13095 | 39508;39509;39510 | chr2:178582353;178582352;178582351 | chr2:179447080;179447079;179447078 |
| Novex-2 | 13162 | 39709;39710;39711 | chr2:178582353;178582352;178582351 | chr2:179447080;179447079;179447078 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | rs373681189  |
0.219 | 0.998 | N | 0.495 | 0.223 | 0.221019684889 | gnomAD-2.1.1 | 2.52E-05 | None | None | None | None | I | None | 8.29E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 1.42328E-04 |
| K/N | rs373681189 |
0.219 | 0.998 | N | 0.495 | 0.223 | 0.221019684889 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| K/N | rs373681189 |
0.219 | 0.998 | N | 0.495 | 0.223 | 0.221019684889 | gnomAD-4.0.0 | 4.53513E-05 | None | None | None | None | I | None | 5.35217E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.26545E-05 | 0 | 1.12421E-04 |
| K/R | None | None | 0.989 | N | 0.432 | 0.227 | 0.335910606209 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6136 | likely_pathogenic | 0.5435 | ambiguous | -0.243 | Destabilizing | 0.992 | D | 0.546 | neutral | None | None | None | None | I |
| K/C | 0.8338 | likely_pathogenic | 0.7861 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | I |
| K/D | 0.8704 | likely_pathogenic | 0.8417 | pathogenic | 0.195 | Stabilizing | 0.998 | D | 0.491 | neutral | None | None | None | None | I |
| K/E | 0.4824 | ambiguous | 0.4072 | ambiguous | 0.235 | Stabilizing | 0.978 | D | 0.462 | neutral | N | 0.501837268 | None | None | I |
| K/F | 0.9247 | likely_pathogenic | 0.909 | pathogenic | -0.325 | Destabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | I |
| K/G | 0.8309 | likely_pathogenic | 0.7951 | pathogenic | -0.492 | Destabilizing | 0.999 | D | 0.465 | neutral | None | None | None | None | I |
| K/H | 0.49 | ambiguous | 0.4512 | ambiguous | -0.807 | Destabilizing | 1.0 | D | 0.499 | neutral | None | None | None | None | I |
| K/I | 0.447 | ambiguous | 0.4159 | ambiguous | 0.349 | Stabilizing | 0.999 | D | 0.59 | neutral | N | 0.516596077 | None | None | I |
| K/L | 0.5681 | likely_pathogenic | 0.4967 | ambiguous | 0.349 | Stabilizing | 0.998 | D | 0.465 | neutral | None | None | None | None | I |
| K/M | 0.3976 | ambiguous | 0.3552 | ambiguous | 0.157 | Stabilizing | 1.0 | D | 0.498 | neutral | None | None | None | None | I |
| K/N | 0.75 | likely_pathogenic | 0.7246 | pathogenic | 0.062 | Stabilizing | 0.998 | D | 0.495 | neutral | N | 0.477280587 | None | None | I |
| K/P | 0.8586 | likely_pathogenic | 0.8342 | pathogenic | 0.181 | Stabilizing | 1.0 | D | 0.529 | neutral | None | None | None | None | I |
| K/Q | 0.2414 | likely_benign | 0.2026 | benign | -0.068 | Destabilizing | 0.775 | D | 0.351 | neutral | N | 0.505955009 | None | None | I |
| K/R | 0.1058 | likely_benign | 0.1015 | benign | -0.181 | Destabilizing | 0.989 | D | 0.432 | neutral | N | 0.500202472 | None | None | I |
| K/S | 0.7277 | likely_pathogenic | 0.6852 | pathogenic | -0.512 | Destabilizing | 0.992 | D | 0.515 | neutral | None | None | None | None | I |
| K/T | 0.3356 | likely_benign | 0.3151 | benign | -0.297 | Destabilizing | 0.998 | D | 0.481 | neutral | N | 0.468949248 | None | None | I |
| K/V | 0.4558 | ambiguous | 0.4287 | ambiguous | 0.181 | Stabilizing | 0.999 | D | 0.489 | neutral | None | None | None | None | I |
| K/W | 0.924 | likely_pathogenic | 0.9018 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| K/Y | 0.8396 | likely_pathogenic | 0.8014 | pathogenic | 0.05 | Stabilizing | 1.0 | D | 0.557 | 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.