Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20251 | 60976;60977;60978 | chr2:178590974;178590973;178590972 | chr2:179455701;179455700;179455699 |
| N2AB | 18610 | 56053;56054;56055 | chr2:178590974;178590973;178590972 | chr2:179455701;179455700;179455699 |
| N2A | 17683 | 53272;53273;53274 | chr2:178590974;178590973;178590972 | chr2:179455701;179455700;179455699 |
| N2B | 11186 | 33781;33782;33783 | chr2:178590974;178590973;178590972 | chr2:179455701;179455700;179455699 |
| Novex-1 | 11311 | 34156;34157;34158 | chr2:178590974;178590973;178590972 | chr2:179455701;179455700;179455699 |
| Novex-2 | 11378 | 34357;34358;34359 | chr2:178590974;178590973;178590972 | chr2:179455701;179455700;179455699 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.999 | N | 0.601 | 0.365 | 0.314716216878 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/M | rs1314635889  |
None | 1.0 | N | 0.583 | 0.413 | 0.407357902709 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/M | rs1314635889 |
None | 1.0 | N | 0.583 | 0.413 | 0.407357902709 | gnomAD-4.0.0 | 6.57575E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47093E-05 | 0 | 0 |
| K/N | rs756340284 |
0.243 | 1.0 | N | 0.684 | 0.382 | 0.1749357433 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| K/N | rs756340284 |
0.243 | 1.0 | N | 0.684 | 0.382 | 0.1749357433 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.9425E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/N | rs756340284 |
0.243 | 1.0 | N | 0.684 | 0.382 | 0.1749357433 | gnomAD-4.0.0 | 2.56335E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.85531E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7769 | likely_pathogenic | 0.8498 | pathogenic | -0.015 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | I |
| K/C | 0.9267 | likely_pathogenic | 0.9399 | pathogenic | -0.335 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| K/D | 0.9182 | likely_pathogenic | 0.9402 | pathogenic | 0.1 | Stabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | I |
| K/E | 0.6582 | likely_pathogenic | 0.7486 | pathogenic | 0.104 | Stabilizing | 0.999 | D | 0.601 | neutral | N | 0.501029192 | None | None | I |
| K/F | 0.9677 | likely_pathogenic | 0.9763 | pathogenic | -0.289 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | I |
| K/G | 0.8513 | likely_pathogenic | 0.8899 | pathogenic | -0.192 | Destabilizing | 1.0 | D | 0.561 | neutral | None | None | None | None | I |
| K/H | 0.6 | likely_pathogenic | 0.6372 | pathogenic | -0.421 | Destabilizing | 1.0 | D | 0.585 | neutral | None | None | None | None | I |
| K/I | 0.7929 | likely_pathogenic | 0.8392 | pathogenic | 0.366 | Stabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| K/L | 0.7495 | likely_pathogenic | 0.8082 | pathogenic | 0.366 | Stabilizing | 1.0 | D | 0.561 | neutral | None | None | None | None | I |
| K/M | 0.644 | likely_pathogenic | 0.7142 | pathogenic | 0.137 | Stabilizing | 1.0 | D | 0.583 | neutral | N | 0.468939702 | None | None | I |
| K/N | 0.8412 | likely_pathogenic | 0.881 | pathogenic | 0.127 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | N | 0.482382695 | None | None | I |
| K/P | 0.8914 | likely_pathogenic | 0.9149 | pathogenic | 0.266 | Stabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | I |
| K/Q | 0.3475 | ambiguous | 0.4299 | ambiguous | -0.028 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | N | 0.509187315 | None | None | I |
| K/R | 0.0937 | likely_benign | 0.1068 | benign | -0.034 | Destabilizing | 0.999 | D | 0.514 | neutral | N | 0.483232865 | None | None | I |
| K/S | 0.8274 | likely_pathogenic | 0.8824 | pathogenic | -0.359 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| K/T | 0.5996 | likely_pathogenic | 0.6822 | pathogenic | -0.21 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.469113832 | None | None | I |
| K/V | 0.744 | likely_pathogenic | 0.8048 | pathogenic | 0.266 | Stabilizing | 1.0 | D | 0.614 | neutral | None | None | None | None | I |
| K/W | 0.9523 | likely_pathogenic | 0.9596 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| K/Y | 0.9019 | likely_pathogenic | 0.9207 | pathogenic | 0.045 | Stabilizing | 1.0 | D | 0.619 | 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.