Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3405 | 10438;10439;10440 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
| N2AB | 3405 | 10438;10439;10440 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
| N2A | 3405 | 10438;10439;10440 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
| N2B | 3359 | 10300;10301;10302 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
| Novex-1 | 3359 | 10300;10301;10302 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
| Novex-2 | 3359 | 10300;10301;10302 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
| Novex-3 | 3405 | 10438;10439;10440 | chr2:178759074;178759073;178759072 | chr2:179623801;179623800;179623799 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs1187665800  |
-0.17 | 0.966 | N | 0.495 | 0.369 | 0.478068462777 | gnomAD-2.1.1 | 2.39E-05 | None | None | None | None | N | None | 0 | 5.78E-05 | None | 0 | 5.45E-05 | None | 0 | None | 0 | 2.65E-05 | 0 |
| E/K | rs1187665800 |
-0.17 | 0.966 | N | 0.495 | 0.369 | 0.478068462777 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78927E-04 |
| E/K | rs1187665800 |
-0.17 | 0.966 | N | 0.495 | 0.369 | 0.478068462777 | gnomAD-4.0.0 | 2.10666E-05 | None | None | None | None | N | None | 1.33269E-05 | 3.33322E-05 | None | 0 | 2.23025E-05 | None | 1.56211E-05 | 1.65071E-04 | 2.03406E-05 | 2.19616E-05 | 3.2002E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.224 | likely_benign | 0.2441 | benign | -0.917 | Destabilizing | 0.961 | D | 0.478 | neutral | N | 0.520717766 | None | None | N |
| E/C | 0.9438 | likely_pathogenic | 0.955 | pathogenic | -0.49 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| E/D | 0.2646 | likely_benign | 0.3174 | benign | -0.648 | Destabilizing | 0.98 | D | 0.459 | neutral | N | 0.503135383 | None | None | N |
| E/F | 0.8788 | likely_pathogenic | 0.9103 | pathogenic | -0.305 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| E/G | 0.29 | likely_benign | 0.3352 | benign | -1.223 | Destabilizing | 0.98 | D | 0.539 | neutral | N | 0.510789735 | None | None | N |
| E/H | 0.6498 | likely_pathogenic | 0.7087 | pathogenic | -0.274 | Destabilizing | 0.999 | D | 0.473 | neutral | None | None | None | None | N |
| E/I | 0.6588 | likely_pathogenic | 0.705 | pathogenic | -0.094 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| E/K | 0.1871 | likely_benign | 0.2107 | benign | -0.338 | Destabilizing | 0.966 | D | 0.495 | neutral | N | 0.50625099 | None | None | N |
| E/L | 0.6494 | likely_pathogenic | 0.6974 | pathogenic | -0.094 | Destabilizing | 0.97 | D | 0.583 | neutral | None | None | None | None | N |
| E/M | 0.6656 | likely_pathogenic | 0.6924 | pathogenic | 0.19 | Stabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | N |
| E/N | 0.441 | ambiguous | 0.5301 | ambiguous | -0.859 | Destabilizing | 0.985 | D | 0.461 | neutral | None | None | None | None | N |
| E/P | 0.9513 | likely_pathogenic | 0.957 | pathogenic | -0.348 | Destabilizing | 0.999 | D | 0.53 | neutral | None | None | None | None | N |
| E/Q | 0.1973 | likely_benign | 0.2239 | benign | -0.744 | Destabilizing | 0.984 | D | 0.479 | neutral | N | 0.515682455 | None | None | N |
| E/R | 0.3078 | likely_benign | 0.3481 | ambiguous | 0.036 | Stabilizing | 0.041 | N | 0.157 | neutral | None | None | None | None | N |
| E/S | 0.3211 | likely_benign | 0.3733 | ambiguous | -1.108 | Destabilizing | 0.985 | D | 0.438 | neutral | None | None | None | None | N |
| E/T | 0.3927 | ambiguous | 0.4471 | ambiguous | -0.846 | Destabilizing | 0.985 | D | 0.473 | neutral | None | None | None | None | N |
| E/V | 0.4053 | ambiguous | 0.4235 | ambiguous | -0.348 | Destabilizing | 0.994 | D | 0.561 | neutral | D | 0.573057838 | None | None | N |
| E/W | 0.9557 | likely_pathogenic | 0.9692 | pathogenic | 0.033 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8145 | likely_pathogenic | 0.8576 | pathogenic | -0.04 | Destabilizing | 0.999 | D | 0.657 | 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.