Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33423 | 100492;100493;100494 | chr2:178536480;178536479;178536478 | chr2:179401207;179401206;179401205 |
| N2AB | 31782 | 95569;95570;95571 | chr2:178536480;178536479;178536478 | chr2:179401207;179401206;179401205 |
| N2A | 30855 | 92788;92789;92790 | chr2:178536480;178536479;178536478 | chr2:179401207;179401206;179401205 |
| N2B | 24358 | 73297;73298;73299 | chr2:178536480;178536479;178536478 | chr2:179401207;179401206;179401205 |
| Novex-1 | 24483 | 73672;73673;73674 | chr2:178536480;178536479;178536478 | chr2:179401207;179401206;179401205 |
| Novex-2 | 24550 | 73873;73874;73875 | chr2:178536480;178536479;178536478 | chr2:179401207;179401206;179401205 |
| 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 | rs376528148  |
0.347 | 0.999 | N | 0.622 | 0.462 | None | gnomAD-2.1.1 | 5.05E-05 | None | None | None | None | I | None | 4.1813E-04 | 9.15E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/E | rs376528148 |
0.347 | 0.999 | N | 0.622 | 0.462 | None | gnomAD-3.1.2 | 1.44545E-04 | None | None | None | None | I | None | 4.82439E-04 | 1.30856E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs376528148 |
0.347 | 0.999 | N | 0.622 | 0.462 | None | gnomAD-4.0.0 | 2.20891E-05 | None | None | None | None | I | None | 3.38158E-04 | 1.04833E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 6.54001E-05 |
| K/N | None | None | 1.0 | N | 0.719 | 0.266 | 0.290962096972 | gnomAD-4.0.0 | 1.66616E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.55855E-05 | 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 | 0.525 | ambiguous | 0.5738 | pathogenic | 0.075 | Stabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | I |
| K/C | 0.8947 | likely_pathogenic | 0.8949 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| K/D | 0.7959 | likely_pathogenic | 0.8507 | pathogenic | -0.059 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| K/E | 0.4041 | ambiguous | 0.4777 | ambiguous | -0.05 | Destabilizing | 0.999 | D | 0.622 | neutral | N | 0.413543493 | None | None | I |
| K/F | 0.9183 | likely_pathogenic | 0.9381 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| K/G | 0.7187 | likely_pathogenic | 0.7423 | pathogenic | -0.114 | Destabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | I |
| K/H | 0.6135 | likely_pathogenic | 0.6231 | pathogenic | -0.294 | Destabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | I |
| K/I | 0.5657 | likely_pathogenic | 0.6362 | pathogenic | 0.495 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| K/L | 0.608 | likely_pathogenic | 0.6616 | pathogenic | 0.495 | Stabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | I |
| K/M | 0.5176 | ambiguous | 0.5611 | ambiguous | 0.142 | Stabilizing | 1.0 | D | 0.586 | neutral | N | 0.515057281 | None | None | I |
| K/N | 0.6581 | likely_pathogenic | 0.7247 | pathogenic | 0.196 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.509880748 | None | None | I |
| K/P | 0.6338 | likely_pathogenic | 0.6964 | pathogenic | 0.382 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| K/Q | 0.2888 | likely_benign | 0.2977 | benign | 0.056 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | N | 0.490948271 | None | None | I |
| K/R | 0.1175 | likely_benign | 0.108 | benign | -0.021 | Destabilizing | 0.999 | D | 0.545 | neutral | N | 0.483560939 | None | None | I |
| K/S | 0.6627 | likely_pathogenic | 0.7152 | pathogenic | -0.224 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | I |
| K/T | 0.3769 | ambiguous | 0.4285 | ambiguous | -0.075 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.457643774 | None | None | I |
| K/V | 0.5109 | ambiguous | 0.559 | ambiguous | 0.382 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| K/W | 0.9448 | likely_pathogenic | 0.9501 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | I |
| K/Y | 0.8712 | likely_pathogenic | 0.8878 | pathogenic | 0.162 | Stabilizing | 1.0 | D | 0.642 | 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.