Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1291 | 4096;4097;4098 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
| N2AB | 1291 | 4096;4097;4098 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
| N2A | 1291 | 4096;4097;4098 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
| N2B | 1245 | 3958;3959;3960 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
| Novex-1 | 1245 | 3958;3959;3960 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
| Novex-2 | 1245 | 3958;3959;3960 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
| Novex-3 | 1291 | 4096;4097;4098 | chr2:178779321;178779320;178779319 | chr2:179644048;179644047;179644046 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs192742099  |
-0.438 | 0.012 | N | 0.357 | 0.278 | None | gnomAD-2.1.1 | 4E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.46E-05 | None | 0 | None | 0 | 0 | 0 |
| S/L | rs192742099 |
-0.438 | 0.012 | N | 0.357 | 0.278 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92308E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/L | rs192742099 |
-0.438 | 0.012 | N | 0.357 | 0.278 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| S/L | rs192742099 |
-0.438 | 0.012 | N | 0.357 | 0.278 | None | gnomAD-4.0.0 | 6.56927E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0391 | likely_benign | 0.0416 | benign | -0.453 | Destabilizing | None | N | 0.144 | neutral | N | 0.436651751 | None | None | N |
| S/C | 0.1259 | likely_benign | 0.1428 | benign | -0.554 | Destabilizing | 0.356 | N | 0.411 | neutral | None | None | None | None | N |
| S/D | 0.8389 | likely_pathogenic | 0.8418 | pathogenic | -1.279 | Destabilizing | 0.072 | N | 0.364 | neutral | None | None | None | None | N |
| S/E | 0.8204 | likely_pathogenic | 0.8095 | pathogenic | -1.327 | Destabilizing | 0.031 | N | 0.369 | neutral | None | None | None | None | N |
| S/F | 0.6421 | likely_pathogenic | 0.6878 | pathogenic | -1.231 | Destabilizing | 0.356 | N | 0.44 | neutral | None | None | None | None | N |
| S/G | 0.1467 | likely_benign | 0.1653 | benign | -0.566 | Destabilizing | 0.016 | N | 0.316 | neutral | None | None | None | None | N |
| S/H | 0.8271 | likely_pathogenic | 0.8344 | pathogenic | -1.232 | Destabilizing | 0.628 | D | 0.418 | neutral | None | None | None | None | N |
| S/I | 0.3676 | ambiguous | 0.395 | ambiguous | -0.265 | Destabilizing | 0.072 | N | 0.361 | neutral | None | None | None | None | N |
| S/K | 0.9529 | likely_pathogenic | 0.9493 | pathogenic | -0.505 | Destabilizing | 0.072 | N | 0.368 | neutral | None | None | None | None | N |
| S/L | 0.2587 | likely_benign | 0.2961 | benign | -0.265 | Destabilizing | 0.012 | N | 0.357 | neutral | N | 0.483955117 | None | None | N |
| S/M | 0.3836 | ambiguous | 0.4228 | ambiguous | 0.245 | Stabilizing | 0.356 | N | 0.417 | neutral | None | None | None | None | N |
| S/N | 0.5232 | ambiguous | 0.5588 | ambiguous | -0.628 | Destabilizing | 0.136 | N | 0.396 | neutral | None | None | None | None | N |
| S/P | 0.1512 | likely_benign | 0.1854 | benign | -0.302 | Destabilizing | None | N | 0.2 | neutral | N | 0.295192083 | None | None | N |
| S/Q | 0.8506 | likely_pathogenic | 0.8462 | pathogenic | -1.031 | Destabilizing | 0.356 | N | 0.456 | neutral | None | None | None | None | N |
| S/R | 0.9411 | likely_pathogenic | 0.9357 | pathogenic | -0.224 | Destabilizing | 0.072 | N | 0.389 | neutral | None | None | None | None | N |
| S/T | 0.1194 | likely_benign | 0.1277 | benign | -0.515 | Destabilizing | 0.012 | N | 0.417 | neutral | N | 0.482590295 | None | None | N |
| S/V | 0.2314 | likely_benign | 0.2365 | benign | -0.302 | Destabilizing | 0.016 | N | 0.355 | neutral | None | None | None | None | N |
| S/W | 0.8088 | likely_pathogenic | 0.8297 | pathogenic | -1.272 | Destabilizing | 0.864 | D | 0.487 | neutral | None | None | None | None | N |
| S/Y | 0.6015 | likely_pathogenic | 0.6296 | pathogenic | -0.902 | Destabilizing | 0.356 | N | 0.434 | 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.