Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19129 | 57610;57611;57612 | chr2:178597697;178597696;178597695 | chr2:179462424;179462423;179462422 |
| N2AB | 17488 | 52687;52688;52689 | chr2:178597697;178597696;178597695 | chr2:179462424;179462423;179462422 |
| N2A | 16561 | 49906;49907;49908 | chr2:178597697;178597696;178597695 | chr2:179462424;179462423;179462422 |
| N2B | 10064 | 30415;30416;30417 | chr2:178597697;178597696;178597695 | chr2:179462424;179462423;179462422 |
| Novex-1 | 10189 | 30790;30791;30792 | chr2:178597697;178597696;178597695 | chr2:179462424;179462423;179462422 |
| Novex-2 | 10256 | 30991;30992;30993 | chr2:178597697;178597696;178597695 | chr2:179462424;179462423;179462422 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/K | rs375305621  |
0.208 | 0.425 | N | 0.276 | 0.153 | 0.141422826196 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| N/K | rs375305621 |
0.208 | 0.425 | N | 0.276 | 0.153 | 0.141422826196 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/K | rs375305621 |
0.208 | 0.425 | N | 0.276 | 0.153 | 0.141422826196 | gnomAD-4.0.0 | 1.17774E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52597E-05 | 0 | 1.60154E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3565 | ambiguous | 0.4014 | ambiguous | -0.671 | Destabilizing | 0.495 | N | 0.385 | neutral | None | None | None | None | N |
| N/C | 0.5 | ambiguous | 0.5188 | ambiguous | 0.269 | Stabilizing | 0.995 | D | 0.46 | neutral | None | None | None | None | N |
| N/D | 0.129 | likely_benign | 0.1509 | benign | -0.181 | Destabilizing | 0.001 | N | 0.133 | neutral | N | 0.376688898 | None | None | N |
| N/E | 0.4201 | ambiguous | 0.4932 | ambiguous | -0.151 | Destabilizing | 0.013 | N | 0.133 | neutral | None | None | None | None | N |
| N/F | 0.7715 | likely_pathogenic | 0.8267 | pathogenic | -0.678 | Destabilizing | 0.981 | D | 0.478 | neutral | None | None | None | None | N |
| N/G | 0.2407 | likely_benign | 0.2409 | benign | -0.947 | Destabilizing | 0.495 | N | 0.288 | neutral | None | None | None | None | N |
| N/H | 0.2037 | likely_benign | 0.2321 | benign | -0.873 | Destabilizing | 0.975 | D | 0.34 | neutral | N | 0.458332822 | None | None | N |
| N/I | 0.6463 | likely_pathogenic | 0.7514 | pathogenic | None | Stabilizing | 0.927 | D | 0.489 | neutral | N | 0.481716996 | None | None | N |
| N/K | 0.4075 | ambiguous | 0.5057 | ambiguous | -0.146 | Destabilizing | 0.425 | N | 0.276 | neutral | N | 0.497271236 | None | None | N |
| N/L | 0.4686 | ambiguous | 0.5407 | ambiguous | None | Stabilizing | 0.828 | D | 0.507 | neutral | None | None | None | None | N |
| N/M | 0.536 | ambiguous | 0.6174 | pathogenic | 0.517 | Stabilizing | 0.995 | D | 0.435 | neutral | None | None | None | None | N |
| N/P | 0.9045 | likely_pathogenic | 0.9446 | pathogenic | -0.194 | Destabilizing | 0.828 | D | 0.467 | neutral | None | None | None | None | N |
| N/Q | 0.3938 | ambiguous | 0.4321 | ambiguous | -0.649 | Destabilizing | 0.704 | D | 0.255 | neutral | None | None | None | None | N |
| N/R | 0.4489 | ambiguous | 0.5297 | ambiguous | -0.138 | Destabilizing | 0.704 | D | 0.312 | neutral | None | None | None | None | N |
| N/S | 0.1477 | likely_benign | 0.155 | benign | -0.538 | Destabilizing | 0.425 | N | 0.297 | neutral | N | 0.497444595 | None | None | N |
| N/T | 0.3659 | ambiguous | 0.4421 | ambiguous | -0.333 | Destabilizing | 0.425 | N | 0.245 | neutral | N | 0.469689128 | None | None | N |
| N/V | 0.6158 | likely_pathogenic | 0.7042 | pathogenic | -0.194 | Destabilizing | 0.828 | D | 0.501 | neutral | None | None | None | None | N |
| N/W | 0.8732 | likely_pathogenic | 0.9057 | pathogenic | -0.511 | Destabilizing | 0.995 | D | 0.527 | neutral | None | None | None | None | N |
| N/Y | 0.308 | likely_benign | 0.375 | ambiguous | -0.308 | Destabilizing | 0.975 | D | 0.451 | neutral | N | 0.481716996 | 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.