Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2277 | 7054;7055;7056 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
| N2AB | 2277 | 7054;7055;7056 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
| N2A | 2277 | 7054;7055;7056 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
| N2B | 2231 | 6916;6917;6918 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
| Novex-1 | 2231 | 6916;6917;6918 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
| Novex-2 | 2231 | 6916;6917;6918 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
| Novex-3 | 2277 | 7054;7055;7056 | chr2:178774435;178774434;178774433 | chr2:179639162;179639161;179639160 |
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/Q | rs373469418  |
-0.157 | 1.0 | N | 0.607 | 0.403 | None | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.65E-05 | 0 |
| E/Q | rs373469418 |
-0.157 | 1.0 | N | 0.607 | 0.403 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| E/Q | rs373469418 |
-0.157 | 1.0 | N | 0.607 | 0.403 | None | gnomAD-4.0.0 | 2.04532E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71199E-05 | 0 | 1.60046E-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 | 0.1716 | likely_benign | 0.1849 | benign | -0.548 | Destabilizing | 0.999 | D | 0.639 | neutral | N | 0.504452519 | None | None | N |
| E/C | 0.8842 | likely_pathogenic | 0.9085 | pathogenic | -0.398 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| E/D | 0.2369 | likely_benign | 0.235 | benign | -0.763 | Destabilizing | 0.999 | D | 0.477 | neutral | N | 0.51364627 | None | None | N |
| E/F | 0.8253 | likely_pathogenic | 0.8425 | pathogenic | -0.042 | Destabilizing | 1.0 | D | 0.632 | neutral | None | None | None | None | N |
| E/G | 0.4092 | ambiguous | 0.4238 | ambiguous | -0.847 | Destabilizing | 1.0 | D | 0.619 | neutral | N | 0.518211779 | None | None | N |
| E/H | 0.6469 | likely_pathogenic | 0.6774 | pathogenic | -0.015 | Destabilizing | 1.0 | D | 0.596 | neutral | None | None | None | None | N |
| E/I | 0.3176 | likely_benign | 0.3436 | ambiguous | 0.245 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| E/K | 0.3503 | ambiguous | 0.3653 | ambiguous | -0.235 | Destabilizing | 0.999 | D | 0.595 | neutral | N | 0.499167265 | None | None | N |
| E/L | 0.4726 | ambiguous | 0.5041 | ambiguous | 0.245 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| E/M | 0.4718 | ambiguous | 0.5044 | ambiguous | 0.343 | Stabilizing | 1.0 | D | 0.595 | neutral | None | None | None | None | N |
| E/N | 0.3991 | ambiguous | 0.4128 | ambiguous | -0.716 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/P | 0.8856 | likely_pathogenic | 0.8848 | pathogenic | 0.002 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| E/Q | 0.2205 | likely_benign | 0.2336 | benign | -0.606 | Destabilizing | 1.0 | D | 0.607 | neutral | N | 0.515823937 | None | None | N |
| E/R | 0.5351 | ambiguous | 0.5559 | ambiguous | 0.118 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| E/S | 0.2273 | likely_benign | 0.2365 | benign | -0.913 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| E/T | 0.1878 | likely_benign | 0.1989 | benign | -0.668 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| E/V | 0.1838 | likely_benign | 0.2022 | benign | 0.002 | Stabilizing | 1.0 | D | 0.651 | neutral | N | 0.500449263 | None | None | N |
| E/W | 0.9491 | likely_pathogenic | 0.9561 | pathogenic | 0.192 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/Y | 0.7724 | likely_pathogenic | 0.7983 | pathogenic | 0.203 | Stabilizing | 1.0 | D | 0.623 | 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.