Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14439 | 43540;43541;43542 | chr2:178632691;178632690;178632689 | chr2:179497418;179497417;179497416 |
| N2AB | 12798 | 38617;38618;38619 | chr2:178632691;178632690;178632689 | chr2:179497418;179497417;179497416 |
| N2A | 11871 | 35836;35837;35838 | chr2:178632691;178632690;178632689 | chr2:179497418;179497417;179497416 |
| N2B | 5374 | 16345;16346;16347 | chr2:178632691;178632690;178632689 | chr2:179497418;179497417;179497416 |
| Novex-1 | 5499 | 16720;16721;16722 | chr2:178632691;178632690;178632689 | chr2:179497418;179497417;179497416 |
| Novex-2 | 5566 | 16921;16922;16923 | chr2:178632691;178632690;178632689 | chr2:179497418;179497417;179497416 |
| 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 | rs200914097  |
-1.253 | 1.0 | D | 0.68 | 0.447 | None | gnomAD-2.1.1 | 5.02E-05 | None | None | None | None | N | None | 3.72702E-04 | 2.83E-05 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 2.36E-05 | 0 |
| R/C | rs200914097 |
-1.253 | 1.0 | D | 0.68 | 0.447 | None | gnomAD-3.1.2 | 1.57936E-04 | None | None | None | None | N | None | 5.55797E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs200914097 |
-1.253 | 1.0 | D | 0.68 | 0.447 | None | gnomAD-4.0.0 | 3.16147E-05 | None | None | None | None | N | None | 4.54351E-04 | 8.33973E-05 | None | 0 | 0 | None | 0 | 0 | 7.63011E-06 | 1.09808E-05 | 3.20379E-05 |
| R/H | rs764117439 |
-1.64 | 0.159 | N | 0.325 | 0.247 | None | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 1.58E-05 | 0 |
| R/H | rs764117439 |
-1.64 | 0.159 | N | 0.325 | 0.247 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 1.3113E-04 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs764117439 |
-1.64 | 0.159 | N | 0.325 | 0.247 | None | gnomAD-4.0.0 | 1.05378E-05 | None | None | None | None | N | None | 1.33583E-05 | 5.00283E-05 | None | 0 | 2.23085E-05 | None | 0 | 0 | 6.78234E-06 | 3.29424E-05 | 1.60164E-05 |
| R/L | rs764117439 |
-0.23 | 0.976 | D | 0.659 | 0.458 | 0.421427970867 | gnomAD-4.0.0 | 6.84359E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52054E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6761 | likely_pathogenic | 0.6705 | pathogenic | -0.915 | Destabilizing | 0.86 | D | 0.627 | neutral | None | None | None | None | N |
| R/C | 0.1814 | likely_benign | 0.1531 | benign | -0.953 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | D | 0.637495836 | None | None | N |
| R/D | 0.9035 | likely_pathogenic | 0.8993 | pathogenic | -0.065 | Destabilizing | 0.956 | D | 0.671 | neutral | None | None | None | None | N |
| R/E | 0.6359 | likely_pathogenic | 0.6229 | pathogenic | 0.101 | Stabilizing | 0.86 | D | 0.585 | neutral | None | None | None | None | N |
| R/F | 0.7148 | likely_pathogenic | 0.6998 | pathogenic | -0.478 | Destabilizing | 0.978 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/G | 0.5379 | ambiguous | 0.5208 | ambiguous | -1.267 | Destabilizing | 0.922 | D | 0.649 | neutral | D | 0.634996416 | None | None | N |
| R/H | 0.1101 | likely_benign | 0.0998 | benign | -1.427 | Destabilizing | 0.159 | N | 0.325 | neutral | N | 0.508279583 | None | None | N |
| R/I | 0.3868 | ambiguous | 0.4146 | ambiguous | 0.049 | Stabilizing | 0.978 | D | 0.708 | prob.delet. | None | None | None | None | N |
| R/K | 0.174 | likely_benign | 0.1749 | benign | -0.887 | Destabilizing | 0.717 | D | 0.554 | neutral | None | None | None | None | N |
| R/L | 0.3677 | ambiguous | 0.3552 | ambiguous | 0.049 | Stabilizing | 0.976 | D | 0.659 | neutral | D | 0.540691374 | None | None | N |
| R/M | 0.5213 | ambiguous | 0.5317 | ambiguous | -0.453 | Destabilizing | 0.998 | D | 0.654 | neutral | None | None | None | None | N |
| R/N | 0.7769 | likely_pathogenic | 0.7825 | pathogenic | -0.527 | Destabilizing | 0.754 | D | 0.599 | neutral | None | None | None | None | N |
| R/P | 0.9704 | likely_pathogenic | 0.97 | pathogenic | -0.252 | Destabilizing | 0.996 | D | 0.695 | prob.neutral | D | 0.636966338 | None | None | N |
| R/Q | 0.1422 | likely_benign | 0.1334 | benign | -0.56 | Destabilizing | 0.956 | D | 0.633 | neutral | None | None | None | None | N |
| R/S | 0.6408 | likely_pathogenic | 0.6324 | pathogenic | -1.321 | Destabilizing | 0.922 | D | 0.651 | neutral | N | 0.491872536 | None | None | N |
| R/T | 0.4063 | ambiguous | 0.4124 | ambiguous | -0.95 | Destabilizing | 0.978 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/V | 0.5213 | ambiguous | 0.5249 | ambiguous | -0.252 | Destabilizing | 0.978 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/W | 0.2729 | likely_benign | 0.2432 | benign | -0.078 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | N |
| R/Y | 0.5436 | ambiguous | 0.5207 | ambiguous | 0.162 | Stabilizing | 0.915 | D | 0.691 | prob.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.