Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32542 | 97849;97850;97851 | chr2:178541453;178541452;178541451 | chr2:179406180;179406179;179406178 |
| N2AB | 30901 | 92926;92927;92928 | chr2:178541453;178541452;178541451 | chr2:179406180;179406179;179406178 |
| N2A | 29974 | 90145;90146;90147 | chr2:178541453;178541452;178541451 | chr2:179406180;179406179;179406178 |
| N2B | 23477 | 70654;70655;70656 | chr2:178541453;178541452;178541451 | chr2:179406180;179406179;179406178 |
| Novex-1 | 23602 | 71029;71030;71031 | chr2:178541453;178541452;178541451 | chr2:179406180;179406179;179406178 |
| Novex-2 | 23669 | 71230;71231;71232 | chr2:178541453;178541452;178541451 | chr2:179406180;179406179;179406178 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs1559104048  |
None | 0.071 | N | 0.357 | 0.201 | 0.144782658237 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/G | rs1559104048 |
None | 0.071 | N | 0.357 | 0.201 | 0.144782658237 | gnomAD-4.0.0 | 1.59198E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02627E-05 |
| R/K | None | None | 0.122 | N | 0.267 | 0.137 | 0.186928172975 | gnomAD-4.0.0 | 6.84343E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52118E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs1449597774 |
None | 0.98 | N | 0.495 | 0.292 | 0.292787519742 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/T | rs1449597774 |
None | 0.98 | N | 0.495 | 0.292 | 0.292787519742 | gnomAD-4.0.0 | 4.33863E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.22995E-05 | None | 0 | 0 | 5.08638E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3603 | ambiguous | 0.4174 | ambiguous | 0.157 | Stabilizing | 0.871 | D | 0.491 | neutral | None | None | None | None | I |
| R/C | 0.2133 | likely_benign | 0.254 | benign | -0.035 | Destabilizing | 1.0 | D | 0.551 | neutral | None | None | None | None | I |
| R/D | 0.5628 | ambiguous | 0.6295 | pathogenic | -0.149 | Destabilizing | 0.996 | D | 0.459 | neutral | None | None | None | None | I |
| R/E | 0.3837 | ambiguous | 0.439 | ambiguous | -0.071 | Destabilizing | 0.97 | D | 0.511 | neutral | None | None | None | None | I |
| R/F | 0.5571 | ambiguous | 0.614 | pathogenic | -0.019 | Destabilizing | 0.999 | D | 0.525 | neutral | None | None | None | None | I |
| R/G | 0.1617 | likely_benign | 0.2059 | benign | -0.052 | Destabilizing | 0.071 | N | 0.357 | neutral | N | 0.349473372 | None | None | I |
| R/H | 0.113 | likely_benign | 0.1308 | benign | -0.673 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | I |
| R/I | 0.4525 | ambiguous | 0.4938 | ambiguous | 0.674 | Stabilizing | 0.998 | D | 0.528 | neutral | N | 0.484369015 | None | None | I |
| R/K | 0.1275 | likely_benign | 0.1317 | benign | 0.034 | Stabilizing | 0.122 | N | 0.267 | neutral | N | 0.407196311 | None | None | I |
| R/L | 0.2475 | likely_benign | 0.2856 | benign | 0.674 | Stabilizing | 0.985 | D | 0.479 | neutral | None | None | None | None | I |
| R/M | 0.2988 | likely_benign | 0.3493 | ambiguous | 0.104 | Stabilizing | 1.0 | D | 0.531 | neutral | None | None | None | None | I |
| R/N | 0.462 | ambiguous | 0.5289 | ambiguous | 0.171 | Stabilizing | 0.985 | D | 0.499 | neutral | None | None | None | None | I |
| R/P | 0.6164 | likely_pathogenic | 0.701 | pathogenic | 0.523 | Stabilizing | 0.999 | D | 0.52 | neutral | None | None | None | None | I |
| R/Q | 0.1155 | likely_benign | 0.1341 | benign | 0.147 | Stabilizing | 0.991 | D | 0.485 | neutral | None | None | None | None | I |
| R/S | 0.4262 | ambiguous | 0.4948 | ambiguous | -0.057 | Destabilizing | 0.961 | D | 0.516 | neutral | N | 0.417815949 | None | None | I |
| R/T | 0.2432 | likely_benign | 0.2892 | benign | 0.159 | Stabilizing | 0.98 | D | 0.495 | neutral | N | 0.444194474 | None | None | I |
| R/V | 0.4779 | ambiguous | 0.5248 | ambiguous | 0.523 | Stabilizing | 0.996 | D | 0.511 | neutral | None | None | None | None | I |
| R/W | 0.2151 | likely_benign | 0.2594 | benign | -0.133 | Destabilizing | 1.0 | D | 0.564 | neutral | None | None | None | None | I |
| R/Y | 0.3833 | ambiguous | 0.4637 | ambiguous | 0.285 | Stabilizing | 0.999 | D | 0.519 | 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.