Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21874 | 65845;65846;65847 | chr2:178583183;178583182;178583181 | chr2:179447910;179447909;179447908 |
| N2AB | 20233 | 60922;60923;60924 | chr2:178583183;178583182;178583181 | chr2:179447910;179447909;179447908 |
| N2A | 19306 | 58141;58142;58143 | chr2:178583183;178583182;178583181 | chr2:179447910;179447909;179447908 |
| N2B | 12809 | 38650;38651;38652 | chr2:178583183;178583182;178583181 | chr2:179447910;179447909;179447908 |
| Novex-1 | 12934 | 39025;39026;39027 | chr2:178583183;178583182;178583181 | chr2:179447910;179447909;179447908 |
| Novex-2 | 13001 | 39226;39227;39228 | chr2:178583183;178583182;178583181 | chr2:179447910;179447909;179447908 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | rs758979983  |
-0.068 | 0.999 | N | 0.584 | 0.264 | 0.484837542351 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 0 | 0 |
| T/N | rs758979983 |
-0.068 | 0.999 | N | 0.584 | 0.264 | 0.484837542351 | gnomAD-4.0.0 | 1.59899E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.8858E-05 | 0 | 0 | 0 | 0 |
| T/P | None | None | 0.999 | N | 0.639 | 0.463 | 0.516437024119 | gnomAD-4.0.0 | 6.85687E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.53601E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs780643085 |
-0.164 | 0.989 | N | 0.459 | 0.186 | 0.249502417897 | gnomAD-2.1.1 | 1.63E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.31518E-04 | None | 0 | 0 | 0 |
| T/S | rs780643085 |
-0.164 | 0.989 | N | 0.459 | 0.186 | 0.249502417897 | gnomAD-4.0.0 | 4.79981E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.15148E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1484 | likely_benign | 0.1214 | benign | -0.423 | Destabilizing | 0.948 | D | 0.483 | neutral | N | 0.478878343 | None | None | I |
| T/C | 0.56 | ambiguous | 0.4813 | ambiguous | -0.431 | Destabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | I |
| T/D | 0.6893 | likely_pathogenic | 0.6114 | pathogenic | 0.391 | Stabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| T/E | 0.4639 | ambiguous | 0.4073 | ambiguous | 0.4 | Stabilizing | 0.999 | D | 0.6 | neutral | None | None | None | None | I |
| T/F | 0.4399 | ambiguous | 0.3047 | benign | -0.604 | Destabilizing | 0.998 | D | 0.638 | neutral | None | None | None | None | I |
| T/G | 0.5978 | likely_pathogenic | 0.5171 | ambiguous | -0.653 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | I |
| T/H | 0.4007 | ambiguous | 0.333 | benign | -0.791 | Destabilizing | 1.0 | D | 0.594 | neutral | None | None | None | None | I |
| T/I | 0.1556 | likely_benign | 0.1119 | benign | 0.088 | Stabilizing | 0.956 | D | 0.498 | neutral | N | 0.480265209 | None | None | I |
| T/K | 0.373 | ambiguous | 0.3184 | benign | -0.338 | Destabilizing | 0.999 | D | 0.611 | neutral | None | None | None | None | I |
| T/L | 0.1249 | likely_benign | 0.095 | benign | 0.088 | Stabilizing | 0.967 | D | 0.487 | neutral | None | None | None | None | I |
| T/M | 0.098 | likely_benign | 0.079 | benign | -0.069 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | I |
| T/N | 0.2464 | likely_benign | 0.2005 | benign | -0.393 | Destabilizing | 0.999 | D | 0.584 | neutral | N | 0.509278607 | None | None | I |
| T/P | 0.2085 | likely_benign | 0.1795 | benign | -0.05 | Destabilizing | 0.999 | D | 0.639 | neutral | N | 0.5102414 | None | None | I |
| T/Q | 0.3302 | likely_benign | 0.2919 | benign | -0.432 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | I |
| T/R | 0.3508 | ambiguous | 0.2924 | benign | -0.185 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | I |
| T/S | 0.2302 | likely_benign | 0.1893 | benign | -0.665 | Destabilizing | 0.989 | D | 0.459 | neutral | N | 0.469528141 | None | None | I |
| T/V | 0.1165 | likely_benign | 0.0942 | benign | -0.05 | Destabilizing | 0.437 | N | 0.203 | neutral | None | None | None | None | I |
| T/W | 0.7766 | likely_pathogenic | 0.6918 | pathogenic | -0.643 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| T/Y | 0.4713 | ambiguous | 0.3726 | ambiguous | -0.332 | Destabilizing | 0.999 | D | 0.633 | 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.