Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32558 | 97897;97898;97899 | chr2:178541405;178541404;178541403 | chr2:179406132;179406131;179406130 |
| N2AB | 30917 | 92974;92975;92976 | chr2:178541405;178541404;178541403 | chr2:179406132;179406131;179406130 |
| N2A | 29990 | 90193;90194;90195 | chr2:178541405;178541404;178541403 | chr2:179406132;179406131;179406130 |
| N2B | 23493 | 70702;70703;70704 | chr2:178541405;178541404;178541403 | chr2:179406132;179406131;179406130 |
| Novex-1 | 23618 | 71077;71078;71079 | chr2:178541405;178541404;178541403 | chr2:179406132;179406131;179406130 |
| Novex-2 | 23685 | 71278;71279;71280 | chr2:178541405;178541404;178541403 | chr2:179406132;179406131;179406130 |
| 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/Q | rs369237346  |
0.285 | 1.0 | N | 0.747 | 0.361 | None | gnomAD-2.1.1 | 1.07667E-04 | None | None | None | None | I | None | 0 | 1.13662E-04 | None | 0 | 0 | None | 3.63733E-04 | None | 0 | 1.0983E-04 | 1.40964E-04 |
| R/Q | rs369237346 |
0.285 | 1.0 | N | 0.747 | 0.361 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07039E-04 | 0 |
| R/Q | rs369237346 |
0.285 | 1.0 | N | 0.747 | 0.361 | None | gnomAD-4.0.0 | 1.22169E-04 | None | None | None | None | I | None | 1.33568E-05 | 6.67579E-05 | None | 0 | 2.23284E-05 | None | 0 | 1.64582E-04 | 1.26345E-04 | 4.07633E-04 | 6.41026E-05 |
| R/W | rs727505090 |
-0.162 | 1.0 | N | 0.762 | 0.473 | 0.546607571196 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/W | rs727505090 |
-0.162 | 1.0 | N | 0.762 | 0.473 | 0.546607571196 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs727505090 |
-0.162 | 1.0 | N | 0.762 | 0.473 | 0.546607571196 | gnomAD-4.0.0 | 4.96078E-06 | None | None | None | None | I | None | 1.33533E-05 | 3.337E-05 | None | 0 | 0 | None | 0 | 0 | 4.23968E-06 | 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 | 0.6682 | likely_pathogenic | 0.7301 | pathogenic | -0.561 | Destabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | I |
| R/C | 0.2676 | likely_benign | 0.3162 | benign | -0.65 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| R/D | 0.8864 | likely_pathogenic | 0.9113 | pathogenic | -0.035 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/E | 0.606 | likely_pathogenic | 0.6594 | pathogenic | 0.119 | Stabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | I |
| R/F | 0.776 | likely_pathogenic | 0.8126 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/G | 0.5768 | likely_pathogenic | 0.6706 | pathogenic | -0.873 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.496932881 | None | None | I |
| R/H | 0.1516 | likely_benign | 0.1838 | benign | -1.192 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| R/I | 0.4834 | ambiguous | 0.5321 | ambiguous | 0.278 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/K | 0.1815 | likely_benign | 0.1811 | benign | -0.429 | Destabilizing | 0.998 | D | 0.542 | neutral | None | None | None | None | I |
| R/L | 0.4456 | ambiguous | 0.5053 | ambiguous | 0.278 | Stabilizing | 1.0 | D | 0.643 | neutral | D | 0.525023559 | None | None | I |
| R/M | 0.5001 | ambiguous | 0.5561 | ambiguous | -0.324 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| R/N | 0.7636 | likely_pathogenic | 0.8107 | pathogenic | -0.281 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| R/P | 0.9675 | likely_pathogenic | 0.9777 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | D | 0.524850201 | None | None | I |
| R/Q | 0.1524 | likely_benign | 0.1774 | benign | -0.281 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.478731122 | None | None | I |
| R/S | 0.6645 | likely_pathogenic | 0.7312 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/T | 0.3958 | ambiguous | 0.4601 | ambiguous | -0.55 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/V | 0.5399 | ambiguous | 0.5792 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/W | 0.3109 | likely_benign | 0.385 | ambiguous | -0.078 | Destabilizing | 1.0 | D | 0.762 | deleterious | N | 0.509651462 | None | None | I |
| R/Y | 0.5571 | ambiguous | 0.6239 | pathogenic | 0.216 | Stabilizing | 1.0 | D | 0.748 | deleterious | 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.