Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33246 | 99961;99962;99963 | chr2:178537471;178537470;178537469 | chr2:179402198;179402197;179402196 |
| N2AB | 31605 | 95038;95039;95040 | chr2:178537471;178537470;178537469 | chr2:179402198;179402197;179402196 |
| N2A | 30678 | 92257;92258;92259 | chr2:178537471;178537470;178537469 | chr2:179402198;179402197;179402196 |
| N2B | 24181 | 72766;72767;72768 | chr2:178537471;178537470;178537469 | chr2:179402198;179402197;179402196 |
| Novex-1 | 24306 | 73141;73142;73143 | chr2:178537471;178537470;178537469 | chr2:179402198;179402197;179402196 |
| Novex-2 | 24373 | 73342;73343;73344 | chr2:178537471;178537470;178537469 | chr2:179402198;179402197;179402196 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | rs1692148720  |
None | 0.995 | N | 0.613 | 0.496 | 0.484109215787 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| E/A | rs1692148720 |
None | 0.995 | N | 0.613 | 0.496 | 0.484109215787 | gnomAD-4.0.0 | 6.57091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.06868E-04 | 0 |
| E/D | rs778016048 |
-0.984 | 0.964 | N | 0.435 | 0.162 | 0.385084120042 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/D | rs778016048 |
-0.984 | 0.964 | N | 0.435 | 0.162 | 0.385084120042 | gnomAD-4.0.0 | 1.59186E-06 | None | None | None | None | N | None | 0 | 2.28854E-05 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.7522 | likely_pathogenic | 0.6874 | pathogenic | -1.006 | Destabilizing | 0.995 | D | 0.613 | neutral | N | 0.491960207 | None | None | N |
| E/C | 0.9897 | likely_pathogenic | 0.9847 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| E/D | 0.6627 | likely_pathogenic | 0.6595 | pathogenic | -1.274 | Destabilizing | 0.964 | D | 0.435 | neutral | N | 0.499792333 | None | None | N |
| E/F | 0.9857 | likely_pathogenic | 0.9809 | pathogenic | -0.557 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | N |
| E/G | 0.8087 | likely_pathogenic | 0.7603 | pathogenic | -1.371 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.493734634 | None | None | N |
| E/H | 0.9434 | likely_pathogenic | 0.9087 | pathogenic | -0.876 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| E/I | 0.9122 | likely_pathogenic | 0.8837 | pathogenic | -0.006 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| E/K | 0.7566 | likely_pathogenic | 0.6524 | pathogenic | -0.926 | Destabilizing | 0.997 | D | 0.567 | neutral | D | 0.526322786 | None | None | N |
| E/L | 0.9385 | likely_pathogenic | 0.9103 | pathogenic | -0.006 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| E/M | 0.9437 | likely_pathogenic | 0.9197 | pathogenic | 0.563 | Stabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | N |
| E/N | 0.9033 | likely_pathogenic | 0.876 | pathogenic | -1.333 | Destabilizing | 0.997 | D | 0.657 | neutral | None | None | None | None | N |
| E/P | 0.9978 | likely_pathogenic | 0.9965 | pathogenic | -0.318 | Destabilizing | 0.992 | D | 0.669 | neutral | None | None | None | None | N |
| E/Q | 0.5439 | ambiguous | 0.4366 | ambiguous | -1.193 | Destabilizing | 0.999 | D | 0.557 | neutral | N | 0.485630331 | None | None | N |
| E/R | 0.8476 | likely_pathogenic | 0.7715 | pathogenic | -0.641 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| E/S | 0.7965 | likely_pathogenic | 0.7495 | pathogenic | -1.66 | Destabilizing | 0.996 | D | 0.597 | neutral | None | None | None | None | N |
| E/T | 0.8154 | likely_pathogenic | 0.7603 | pathogenic | -1.362 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| E/V | 0.8118 | likely_pathogenic | 0.7638 | pathogenic | -0.318 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | N | 0.48613731 | None | None | N |
| E/W | 0.9949 | likely_pathogenic | 0.993 | pathogenic | -0.35 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| E/Y | 0.9775 | likely_pathogenic | 0.9685 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
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.