Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23990 | 72193;72194;72195 | chr2:178574164;178574163;178574162 | chr2:179438891;179438890;179438889 |
| N2AB | 22349 | 67270;67271;67272 | chr2:178574164;178574163;178574162 | chr2:179438891;179438890;179438889 |
| N2A | 21422 | 64489;64490;64491 | chr2:178574164;178574163;178574162 | chr2:179438891;179438890;179438889 |
| N2B | 14925 | 44998;44999;45000 | chr2:178574164;178574163;178574162 | chr2:179438891;179438890;179438889 |
| Novex-1 | 15050 | 45373;45374;45375 | chr2:178574164;178574163;178574162 | chr2:179438891;179438890;179438889 |
| Novex-2 | 15117 | 45574;45575;45576 | chr2:178574164;178574163;178574162 | chr2:179438891;179438890;179438889 |
| 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/R | rs540800852  |
-0.487 | 0.934 | N | 0.391 | 0.205 | 0.446410834509 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/R | rs540800852 |
-0.487 | 0.934 | N | 0.391 | 0.205 | 0.446410834509 | gnomAD-4.0.0 | 1.59173E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02462E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1106 | likely_benign | 0.1193 | benign | -0.836 | Destabilizing | 0.454 | N | 0.311 | neutral | N | 0.470963938 | None | None | N |
| T/C | 0.5841 | likely_pathogenic | 0.5854 | pathogenic | -0.336 | Destabilizing | 0.998 | D | 0.392 | neutral | None | None | None | None | N |
| T/D | 0.611 | likely_pathogenic | 0.6333 | pathogenic | -0.249 | Destabilizing | 0.728 | D | 0.318 | neutral | None | None | None | None | N |
| T/E | 0.4149 | ambiguous | 0.4505 | ambiguous | -0.252 | Destabilizing | 0.842 | D | 0.375 | neutral | None | None | None | None | N |
| T/F | 0.4147 | ambiguous | 0.4322 | ambiguous | -0.895 | Destabilizing | 0.974 | D | 0.433 | neutral | None | None | None | None | N |
| T/G | 0.3736 | ambiguous | 0.377 | ambiguous | -1.093 | Destabilizing | 0.728 | D | 0.369 | neutral | None | None | None | None | N |
| T/H | 0.3726 | ambiguous | 0.4042 | ambiguous | -1.315 | Destabilizing | 0.974 | D | 0.405 | neutral | None | None | None | None | N |
| T/I | 0.189 | likely_benign | 0.1954 | benign | -0.241 | Destabilizing | 0.051 | N | 0.222 | neutral | N | 0.461377512 | None | None | N |
| T/K | 0.2604 | likely_benign | 0.2985 | benign | -0.78 | Destabilizing | 0.801 | D | 0.385 | neutral | N | 0.491638917 | None | None | N |
| T/L | 0.1194 | likely_benign | 0.1246 | benign | -0.241 | Destabilizing | 0.525 | D | 0.351 | neutral | None | None | None | None | N |
| T/M | 0.0945 | likely_benign | 0.1069 | benign | 0.063 | Stabilizing | 0.974 | D | 0.388 | neutral | None | None | None | None | N |
| T/N | 0.1874 | likely_benign | 0.1974 | benign | -0.631 | Destabilizing | 0.016 | N | 0.183 | neutral | None | None | None | None | N |
| T/P | 0.279 | likely_benign | 0.2828 | benign | -0.407 | Destabilizing | 0.966 | D | 0.398 | neutral | N | 0.474130716 | None | None | N |
| T/Q | 0.2584 | likely_benign | 0.2841 | benign | -0.768 | Destabilizing | 0.974 | D | 0.387 | neutral | None | None | None | None | N |
| T/R | 0.2395 | likely_benign | 0.2752 | benign | -0.517 | Destabilizing | 0.934 | D | 0.391 | neutral | N | 0.505010859 | None | None | N |
| T/S | 0.1549 | likely_benign | 0.1632 | benign | -0.884 | Destabilizing | 0.136 | N | 0.149 | neutral | N | 0.475498816 | None | None | N |
| T/V | 0.145 | likely_benign | 0.1464 | benign | -0.407 | Destabilizing | 0.525 | D | 0.291 | neutral | None | None | None | None | N |
| T/W | 0.7578 | likely_pathogenic | 0.7831 | pathogenic | -0.859 | Destabilizing | 0.998 | D | 0.531 | neutral | None | None | None | None | N |
| T/Y | 0.4726 | ambiguous | 0.4835 | ambiguous | -0.65 | Destabilizing | 0.991 | D | 0.427 | 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.