Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19244 | 57955;57956;57957 | chr2:178595624;178595623;178595622 | chr2:179460351;179460350;179460349 |
| N2AB | 17603 | 53032;53033;53034 | chr2:178595624;178595623;178595622 | chr2:179460351;179460350;179460349 |
| N2A | 16676 | 50251;50252;50253 | chr2:178595624;178595623;178595622 | chr2:179460351;179460350;179460349 |
| N2B | 10179 | 30760;30761;30762 | chr2:178595624;178595623;178595622 | chr2:179460351;179460350;179460349 |
| Novex-1 | 10304 | 31135;31136;31137 | chr2:178595624;178595623;178595622 | chr2:179460351;179460350;179460349 |
| Novex-2 | 10371 | 31336;31337;31338 | chr2:178595624;178595623;178595622 | chr2:179460351;179460350;179460349 |
| 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/P | rs796304694  |
-0.476 | 0.859 | N | 0.649 | 0.332 | 0.369309618794 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| T/P | rs796304694 |
-0.476 | 0.859 | N | 0.649 | 0.332 | 0.369309618794 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/P | rs796304694 |
-0.476 | 0.859 | N | 0.649 | 0.332 | 0.369309618794 | gnomAD-4.0.0 | 2.49655E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.40715E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0899 | likely_benign | 0.0896 | benign | -0.493 | Destabilizing | 0.055 | N | 0.433 | neutral | N | 0.49455151 | None | None | N |
| T/C | 0.3862 | ambiguous | 0.3542 | ambiguous | -0.241 | Destabilizing | 0.909 | D | 0.637 | neutral | None | None | None | None | N |
| T/D | 0.5144 | ambiguous | 0.5082 | ambiguous | -0.035 | Destabilizing | 0.726 | D | 0.628 | neutral | None | None | None | None | N |
| T/E | 0.4291 | ambiguous | 0.4292 | ambiguous | -0.093 | Destabilizing | 0.726 | D | 0.614 | neutral | None | None | None | None | N |
| T/F | 0.2368 | likely_benign | 0.242 | benign | -0.809 | Destabilizing | 0.567 | D | 0.696 | prob.neutral | None | None | None | None | N |
| T/G | 0.358 | ambiguous | 0.3526 | ambiguous | -0.674 | Destabilizing | 0.431 | N | 0.637 | neutral | None | None | None | None | N |
| T/H | 0.3196 | likely_benign | 0.3009 | benign | -0.964 | Destabilizing | 0.968 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/I | 0.0946 | likely_benign | 0.1027 | benign | -0.124 | Destabilizing | 0.02 | N | 0.534 | neutral | N | 0.496359664 | None | None | N |
| T/K | 0.3709 | ambiguous | 0.3893 | ambiguous | -0.54 | Destabilizing | 0.726 | D | 0.612 | neutral | None | None | None | None | N |
| T/L | 0.0925 | likely_benign | 0.0949 | benign | -0.124 | Destabilizing | 0.072 | N | 0.469 | neutral | None | None | None | None | N |
| T/M | 0.0854 | likely_benign | 0.084 | benign | 0.148 | Stabilizing | 0.567 | D | 0.657 | neutral | None | None | None | None | N |
| T/N | 0.1426 | likely_benign | 0.1291 | benign | -0.292 | Destabilizing | 0.859 | D | 0.529 | neutral | N | 0.487470822 | None | None | N |
| T/P | 0.2422 | likely_benign | 0.2533 | benign | -0.216 | Destabilizing | 0.859 | D | 0.649 | neutral | N | 0.487164178 | None | None | N |
| T/Q | 0.3139 | likely_benign | 0.3097 | benign | -0.536 | Destabilizing | 0.89 | D | 0.657 | neutral | None | None | None | None | N |
| T/R | 0.3262 | likely_benign | 0.3471 | ambiguous | -0.225 | Destabilizing | 0.726 | D | 0.655 | neutral | None | None | None | None | N |
| T/S | 0.1321 | likely_benign | 0.122 | benign | -0.523 | Destabilizing | 0.22 | N | 0.461 | neutral | N | 0.47858198 | None | None | N |
| T/V | 0.0764 | likely_benign | 0.0812 | benign | -0.216 | Destabilizing | None | N | 0.266 | neutral | None | None | None | None | N |
| T/W | 0.6457 | likely_pathogenic | 0.6135 | pathogenic | -0.777 | Destabilizing | 0.968 | D | 0.724 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3242 | likely_benign | 0.3065 | benign | -0.53 | Destabilizing | 0.726 | D | 0.697 | prob.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.