Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8382 | 25369;25370;25371 | chr2:178717730;178717729;178717728 | chr2:179582457;179582456;179582455 |
| N2AB | 8065 | 24418;24419;24420 | chr2:178717730;178717729;178717728 | chr2:179582457;179582456;179582455 |
| N2A | 7138 | 21637;21638;21639 | chr2:178717730;178717729;178717728 | chr2:179582457;179582456;179582455 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs776519143  |
-0.629 | 0.282 | N | 0.343 | 0.402 | 0.69279764771 | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | I | None | 0 | 8.73E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.07724E-04 | 0 |
| R/C | rs776519143 |
-0.629 | 0.282 | N | 0.343 | 0.402 | 0.69279764771 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs776519143 |
-0.629 | 0.282 | N | 0.343 | 0.402 | 0.69279764771 | gnomAD-4.0.0 | 1.48784E-05 | None | None | None | None | I | None | 1.33629E-05 | 6.67022E-05 | None | 0 | 0 | None | 1.56534E-05 | 0 | 1.44123E-05 | 1.09893E-05 | 0 |
| R/H | rs199598066 |
-1.384 | 0.999 | D | 0.481 | 0.303 | None | gnomAD-2.1.1 | 2.15706E-04 | None | None | None | None | I | None | 0 | 1.70474E-04 | None | 0 | 5.15E-05 | None | 0 | None | 4.01E-05 | 4.02399E-04 | 1.41764E-04 |
| R/H | rs199598066 |
-1.384 | 0.999 | D | 0.481 | 0.303 | None | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.76439E-04 | 0 | 4.78469E-04 |
| R/H | rs199598066 |
-1.384 | 0.999 | D | 0.481 | 0.303 | None | gnomAD-4.0.0 | 1.45686E-04 | None | None | None | None | I | None | 1.33565E-05 | 1.8348E-04 | None | 0 | 2.23015E-05 | None | 1.40876E-04 | 0 | 1.75495E-04 | 0 | 9.61169E-05 |
| R/S | rs776519143 |
None | 0.921 | N | 0.366 | 0.319 | 0.475272412942 | gnomAD-4.0.0 | 4.1067E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49822E-06 | 0 | 1.65739E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5659 | likely_pathogenic | 0.6846 | pathogenic | -0.995 | Destabilizing | 0.143 | N | 0.251 | neutral | None | None | None | None | I |
| R/C | 0.2821 | likely_benign | 0.3537 | ambiguous | -0.944 | Destabilizing | 0.282 | N | 0.343 | neutral | N | 0.512915299 | None | None | I |
| R/D | 0.8127 | likely_pathogenic | 0.8843 | pathogenic | -0.406 | Destabilizing | 0.984 | D | 0.504 | neutral | None | None | None | None | I |
| R/E | 0.5161 | ambiguous | 0.6374 | pathogenic | -0.245 | Destabilizing | 0.947 | D | 0.351 | neutral | None | None | None | None | I |
| R/F | 0.6623 | likely_pathogenic | 0.7813 | pathogenic | -0.562 | Destabilizing | 0.976 | D | 0.494 | neutral | None | None | None | None | I |
| R/G | 0.4571 | ambiguous | 0.5918 | pathogenic | -1.357 | Destabilizing | 0.069 | N | 0.286 | neutral | N | 0.484669279 | None | None | I |
| R/H | 0.1212 | likely_benign | 0.1617 | benign | -1.571 | Destabilizing | 0.999 | D | 0.481 | neutral | D | 0.526440216 | None | None | I |
| R/I | 0.3944 | ambiguous | 0.5266 | ambiguous | 0.003 | Stabilizing | 0.86 | D | 0.493 | neutral | None | None | None | None | I |
| R/K | 0.1839 | likely_benign | 0.2368 | benign | -1.137 | Destabilizing | 0.747 | D | 0.363 | neutral | None | None | None | None | I |
| R/L | 0.3611 | ambiguous | 0.4848 | ambiguous | 0.003 | Stabilizing | 0.03 | N | 0.279 | neutral | N | 0.517898091 | None | None | I |
| R/M | 0.4463 | ambiguous | 0.5778 | pathogenic | -0.334 | Destabilizing | 0.977 | D | 0.481 | neutral | None | None | None | None | I |
| R/N | 0.6903 | likely_pathogenic | 0.7907 | pathogenic | -0.723 | Destabilizing | 0.984 | D | 0.349 | neutral | None | None | None | None | I |
| R/P | 0.8836 | likely_pathogenic | 0.9229 | pathogenic | -0.31 | Destabilizing | 0.997 | D | 0.529 | neutral | N | 0.496025585 | None | None | I |
| R/Q | 0.1314 | likely_benign | 0.1686 | benign | -0.741 | Destabilizing | 0.993 | D | 0.445 | neutral | None | None | None | None | I |
| R/S | 0.6164 | likely_pathogenic | 0.7373 | pathogenic | -1.449 | Destabilizing | 0.921 | D | 0.366 | neutral | N | 0.517492659 | None | None | I |
| R/T | 0.4057 | ambiguous | 0.5302 | ambiguous | -1.089 | Destabilizing | 0.143 | N | 0.228 | neutral | None | None | None | None | I |
| R/V | 0.469 | ambiguous | 0.5958 | pathogenic | -0.31 | Destabilizing | 0.647 | D | 0.407 | neutral | None | None | None | None | I |
| R/W | 0.2571 | likely_benign | 0.3623 | ambiguous | -0.185 | Destabilizing | 1.0 | D | 0.47 | neutral | None | None | None | None | I |
| R/Y | 0.4811 | ambiguous | 0.6081 | pathogenic | 0.076 | Stabilizing | 0.996 | D | 0.477 | neutral | None | None | None | None | I |
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.