Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23782 | 71569;71570;71571 | chr2:178574788;178574787;178574786 | chr2:179439515;179439514;179439513 |
| N2AB | 22141 | 66646;66647;66648 | chr2:178574788;178574787;178574786 | chr2:179439515;179439514;179439513 |
| N2A | 21214 | 63865;63866;63867 | chr2:178574788;178574787;178574786 | chr2:179439515;179439514;179439513 |
| N2B | 14717 | 44374;44375;44376 | chr2:178574788;178574787;178574786 | chr2:179439515;179439514;179439513 |
| Novex-1 | 14842 | 44749;44750;44751 | chr2:178574788;178574787;178574786 | chr2:179439515;179439514;179439513 |
| Novex-2 | 14909 | 44950;44951;44952 | chr2:178574788;178574787;178574786 | chr2:179439515;179439514;179439513 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1444831145  |
-0.615 | 1.0 | N | 0.595 | 0.442 | 0.592827455569 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| I/T | rs1444831145 |
-0.615 | 1.0 | N | 0.595 | 0.442 | 0.592827455569 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/T | rs1444831145 |
-0.615 | 1.0 | N | 0.595 | 0.442 | 0.592827455569 | gnomAD-4.0.0 | 1.11651E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44199E-05 | 0 | 1.60308E-05 |
| I/V | rs2154171775 |
None | 0.993 | N | 0.311 | 0.242 | 0.512249151391 | gnomAD-4.0.0 | 1.59504E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43662E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7707 | likely_pathogenic | 0.7733 | pathogenic | -0.66 | Destabilizing | 0.999 | D | 0.509 | neutral | None | None | None | None | I |
| I/C | 0.9161 | likely_pathogenic | 0.9243 | pathogenic | -0.722 | Destabilizing | 1.0 | D | 0.619 | neutral | None | None | None | None | I |
| I/D | 0.9848 | likely_pathogenic | 0.9892 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | I |
| I/E | 0.9534 | likely_pathogenic | 0.9683 | pathogenic | 0.022 | Stabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | I |
| I/F | 0.5011 | ambiguous | 0.492 | ambiguous | -0.528 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| I/G | 0.9382 | likely_pathogenic | 0.9446 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
| I/H | 0.9329 | likely_pathogenic | 0.9414 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| I/K | 0.8838 | likely_pathogenic | 0.9089 | pathogenic | -0.357 | Destabilizing | 1.0 | D | 0.611 | neutral | N | 0.421413615 | None | None | I |
| I/L | 0.2721 | likely_benign | 0.2958 | benign | -0.284 | Destabilizing | 0.993 | D | 0.301 | neutral | N | 0.468975488 | None | None | I |
| I/M | 0.2503 | likely_benign | 0.2626 | benign | -0.425 | Destabilizing | 1.0 | D | 0.618 | neutral | N | 0.502818703 | None | None | I |
| I/N | 0.8066 | likely_pathogenic | 0.8399 | pathogenic | -0.209 | Destabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | I |
| I/P | 0.8993 | likely_pathogenic | 0.9062 | pathogenic | -0.376 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | I |
| I/Q | 0.8628 | likely_pathogenic | 0.8861 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | I |
| I/R | 0.8414 | likely_pathogenic | 0.8632 | pathogenic | 0.138 | Stabilizing | 1.0 | D | 0.635 | neutral | N | 0.446194629 | None | None | I |
| I/S | 0.734 | likely_pathogenic | 0.7539 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.579 | neutral | None | None | None | None | I |
| I/T | 0.7651 | likely_pathogenic | 0.7859 | pathogenic | -0.683 | Destabilizing | 1.0 | D | 0.595 | neutral | N | 0.392261357 | None | None | I |
| I/V | 0.2517 | likely_benign | 0.2486 | benign | -0.376 | Destabilizing | 0.993 | D | 0.311 | neutral | N | 0.448098784 | None | None | I |
| I/W | 0.9549 | likely_pathogenic | 0.9483 | pathogenic | -0.543 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| I/Y | 0.8786 | likely_pathogenic | 0.8802 | pathogenic | -0.303 | Destabilizing | 1.0 | D | 0.621 | 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.