Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32966 | 99121;99122;99123 | chr2:178539039;178539038;178539037 | chr2:179403766;179403765;179403764 |
| N2AB | 31325 | 94198;94199;94200 | chr2:178539039;178539038;178539037 | chr2:179403766;179403765;179403764 |
| N2A | 30398 | 91417;91418;91419 | chr2:178539039;178539038;178539037 | chr2:179403766;179403765;179403764 |
| N2B | 23901 | 71926;71927;71928 | chr2:178539039;178539038;178539037 | chr2:179403766;179403765;179403764 |
| Novex-1 | 24026 | 72301;72302;72303 | chr2:178539039;178539038;178539037 | chr2:179403766;179403765;179403764 |
| Novex-2 | 24093 | 72502;72503;72504 | chr2:178539039;178539038;178539037 | chr2:179403766;179403765;179403764 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 1.0 | N | 0.56 | 0.329 | 0.311387274539 | gnomAD-4.0.0 | 6.84234E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51953E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs1338187239  |
-1.394 | 1.0 | N | 0.703 | 0.362 | 0.290962096972 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs1338187239 |
-1.394 | 1.0 | N | 0.703 | 0.362 | 0.290962096972 | gnomAD-4.0.0 | 2.0527E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 1.79901E-06 | 0 | 0 |
| A/V | rs759090913 |
-0.29 | 1.0 | N | 0.645 | 0.442 | 0.408036853922 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5279 | ambiguous | 0.5285 | ambiguous | -0.935 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| A/D | 0.717 | likely_pathogenic | 0.7368 | pathogenic | -1.796 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.497740957 | None | None | N |
| A/E | 0.594 | likely_pathogenic | 0.6191 | pathogenic | -1.779 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| A/F | 0.6428 | likely_pathogenic | 0.6781 | pathogenic | -1.091 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| A/G | 0.2596 | likely_benign | 0.2805 | benign | -1.409 | Destabilizing | 1.0 | D | 0.538 | neutral | N | 0.464244459 | None | None | N |
| A/H | 0.6917 | likely_pathogenic | 0.7231 | pathogenic | -1.692 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| A/I | 0.5032 | ambiguous | 0.5135 | ambiguous | -0.382 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/K | 0.7053 | likely_pathogenic | 0.7265 | pathogenic | -1.443 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| A/L | 0.3691 | ambiguous | 0.3948 | ambiguous | -0.382 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| A/M | 0.3422 | ambiguous | 0.3613 | ambiguous | -0.242 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| A/N | 0.4748 | ambiguous | 0.4953 | ambiguous | -1.239 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/P | 0.9895 | likely_pathogenic | 0.9916 | pathogenic | -0.58 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | N | 0.484664101 | None | None | N |
| A/Q | 0.5101 | ambiguous | 0.5345 | ambiguous | -1.347 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| A/R | 0.5928 | likely_pathogenic | 0.6173 | pathogenic | -1.108 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/S | 0.1245 | likely_benign | 0.1256 | benign | -1.562 | Destabilizing | 1.0 | D | 0.56 | neutral | N | 0.424627278 | None | None | N |
| A/T | 0.1219 | likely_benign | 0.1253 | benign | -1.455 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.392874645 | None | None | N |
| A/V | 0.2351 | likely_benign | 0.2395 | benign | -0.58 | Destabilizing | 1.0 | D | 0.645 | neutral | N | 0.429534453 | None | None | N |
| A/W | 0.934 | likely_pathogenic | 0.9418 | pathogenic | -1.57 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| A/Y | 0.7721 | likely_pathogenic | 0.7961 | pathogenic | -1.142 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | 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.