Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34174 | 102745;102746;102747 | chr2:178534095;178534094;178534093 | chr2:179398822;179398821;179398820 |
| N2AB | 32533 | 97822;97823;97824 | chr2:178534095;178534094;178534093 | chr2:179398822;179398821;179398820 |
| N2A | 31606 | 95041;95042;95043 | chr2:178534095;178534094;178534093 | chr2:179398822;179398821;179398820 |
| N2B | 25109 | 75550;75551;75552 | chr2:178534095;178534094;178534093 | chr2:179398822;179398821;179398820 |
| Novex-1 | 25234 | 75925;75926;75927 | chr2:178534095;178534094;178534093 | chr2:179398822;179398821;179398820 |
| Novex-2 | 25301 | 76126;76127;76128 | chr2:178534095;178534094;178534093 | chr2:179398822;179398821;179398820 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.165 | N | 0.259 | 0.083 | 0.40318662893 | gnomAD-4.0.0 | 1.59099E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85775E-06 | 0 | 0 |
| V/I | rs200430493  |
-0.112 | 0.004 | N | 0.143 | 0.083 | None | gnomAD-2.1.1 | 8.92E-05 | None | None | None | None | I | None | 4.13223E-04 | 5.65E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.59E-05 | 2.80741E-04 |
| V/I | rs200430493 |
-0.112 | 0.004 | N | 0.143 | 0.083 | None | gnomAD-3.1.2 | 1.77412E-04 | None | None | None | None | I | None | 4.58384E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17592E-04 | 0 | 0 |
| V/I | rs200430493 |
-0.112 | 0.004 | N | 0.143 | 0.083 | None | gnomAD-4.0.0 | 8.30329E-05 | None | None | None | None | I | None | 3.20342E-04 | 1.00007E-04 | None | 0 | 2.22757E-05 | None | 0 | 1.64366E-04 | 8.05188E-05 | 2.19582E-05 | 8.00487E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.406 | ambiguous | 0.4226 | ambiguous | -0.425 | Destabilizing | 0.165 | N | 0.259 | neutral | N | 0.456168401 | None | None | I |
| V/C | 0.8469 | likely_pathogenic | 0.8822 | pathogenic | -0.836 | Destabilizing | 0.981 | D | 0.337 | neutral | None | None | None | None | I |
| V/D | 0.6403 | likely_pathogenic | 0.6714 | pathogenic | -0.296 | Destabilizing | 0.193 | N | 0.433 | neutral | N | 0.37462724 | None | None | I |
| V/E | 0.5652 | likely_pathogenic | 0.5823 | pathogenic | -0.392 | Destabilizing | 0.388 | N | 0.389 | neutral | None | None | None | None | I |
| V/F | 0.2733 | likely_benign | 0.3029 | benign | -0.666 | Destabilizing | 0.81 | D | 0.351 | neutral | N | 0.475447596 | None | None | I |
| V/G | 0.4046 | ambiguous | 0.4375 | ambiguous | -0.51 | Destabilizing | 0.324 | N | 0.375 | neutral | N | 0.333945693 | None | None | I |
| V/H | 0.7916 | likely_pathogenic | 0.8049 | pathogenic | 0.045 | Stabilizing | 0.944 | D | 0.407 | neutral | None | None | None | None | I |
| V/I | 0.1017 | likely_benign | 0.1015 | benign | -0.334 | Destabilizing | 0.004 | N | 0.143 | neutral | N | 0.475447596 | None | None | I |
| V/K | 0.6017 | likely_pathogenic | 0.6189 | pathogenic | -0.434 | Destabilizing | 0.388 | N | 0.385 | neutral | None | None | None | None | I |
| V/L | 0.3145 | likely_benign | 0.3141 | benign | -0.334 | Destabilizing | 0.08 | N | 0.259 | neutral | N | 0.456861835 | None | None | I |
| V/M | 0.221 | likely_benign | 0.2237 | benign | -0.648 | Destabilizing | 0.69 | D | 0.318 | neutral | None | None | None | None | I |
| V/N | 0.442 | ambiguous | 0.4561 | ambiguous | -0.308 | Destabilizing | 0.008 | N | 0.267 | neutral | None | None | None | None | I |
| V/P | 0.7408 | likely_pathogenic | 0.7453 | pathogenic | -0.336 | Destabilizing | 0.932 | D | 0.403 | neutral | None | None | None | None | I |
| V/Q | 0.5371 | ambiguous | 0.5317 | ambiguous | -0.486 | Destabilizing | 0.818 | D | 0.391 | neutral | None | None | None | None | I |
| V/R | 0.5226 | ambiguous | 0.5433 | ambiguous | 0.028 | Stabilizing | 0.818 | D | 0.441 | neutral | None | None | None | None | I |
| V/S | 0.3915 | ambiguous | 0.4021 | ambiguous | -0.642 | Destabilizing | 0.241 | N | 0.281 | neutral | None | None | None | None | I |
| V/T | 0.3879 | ambiguous | 0.3956 | ambiguous | -0.642 | Destabilizing | 0.008 | N | 0.135 | neutral | None | None | None | None | I |
| V/W | 0.8837 | likely_pathogenic | 0.9029 | pathogenic | -0.723 | Destabilizing | 0.981 | D | 0.529 | neutral | None | None | None | None | I |
| V/Y | 0.6695 | likely_pathogenic | 0.7086 | pathogenic | -0.461 | Destabilizing | 0.818 | D | 0.343 | 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.