Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3158 | 9697;9698;9699 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
| N2AB | 3158 | 9697;9698;9699 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
| N2A | 3158 | 9697;9698;9699 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
| N2B | 3112 | 9559;9560;9561 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
| Novex-1 | 3112 | 9559;9560;9561 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
| Novex-2 | 3112 | 9559;9560;9561 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
| Novex-3 | 3158 | 9697;9698;9699 | chr2:178766612;178766611;178766610 | chr2:179631339;179631338;179631337 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs748114137  |
-1.336 | 0.997 | D | 0.681 | 0.734 | 0.784949373506 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| V/F | rs748114137 |
-1.336 | 0.997 | D | 0.681 | 0.734 | 0.784949373506 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 2.08943E-04 | 0 |
| V/F | rs748114137 |
-1.336 | 0.997 | D | 0.681 | 0.734 | 0.784949373506 | gnomAD-4.0.0 | 1.55181E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03778E-05 | 1.09907E-05 | 0 |
| V/L | None | None | 0.863 | D | 0.483 | 0.537 | 0.669649519912 | gnomAD-4.0.0 | 6.8535E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01114E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7322 | likely_pathogenic | 0.73 | pathogenic | -1.735 | Destabilizing | 0.046 | N | 0.25 | neutral | N | 0.516119275 | None | None | I |
| V/C | 0.9605 | likely_pathogenic | 0.9657 | pathogenic | -1.25 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| V/D | 0.9616 | likely_pathogenic | 0.9772 | pathogenic | -1.913 | Destabilizing | 0.991 | D | 0.713 | prob.delet. | D | 0.65475327 | None | None | I |
| V/E | 0.9245 | likely_pathogenic | 0.9456 | pathogenic | -1.891 | Destabilizing | 0.986 | D | 0.699 | prob.neutral | None | None | None | None | I |
| V/F | 0.7319 | likely_pathogenic | 0.8706 | pathogenic | -1.342 | Destabilizing | 0.997 | D | 0.681 | prob.neutral | D | 0.653139905 | None | None | I |
| V/G | 0.7559 | likely_pathogenic | 0.7936 | pathogenic | -2.075 | Highly Destabilizing | 0.964 | D | 0.677 | prob.neutral | D | 0.654138705 | None | None | I |
| V/H | 0.9831 | likely_pathogenic | 0.9912 | pathogenic | -1.618 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | I |
| V/I | 0.153 | likely_benign | 0.2248 | benign | -0.878 | Destabilizing | 0.863 | D | 0.509 | neutral | N | 0.520171548 | None | None | I |
| V/K | 0.9598 | likely_pathogenic | 0.9753 | pathogenic | -1.412 | Destabilizing | 0.986 | D | 0.697 | prob.neutral | None | None | None | None | I |
| V/L | 0.7433 | likely_pathogenic | 0.8725 | pathogenic | -0.878 | Destabilizing | 0.863 | D | 0.483 | neutral | D | 0.648918988 | None | None | I |
| V/M | 0.6529 | likely_pathogenic | 0.7975 | pathogenic | -0.711 | Destabilizing | 0.998 | D | 0.688 | prob.neutral | None | None | None | None | I |
| V/N | 0.9237 | likely_pathogenic | 0.9573 | pathogenic | -1.28 | Destabilizing | 0.993 | D | 0.735 | prob.delet. | None | None | None | None | I |
| V/P | 0.9677 | likely_pathogenic | 0.995 | pathogenic | -1.131 | Destabilizing | 0.993 | D | 0.687 | prob.neutral | None | None | None | None | I |
| V/Q | 0.9463 | likely_pathogenic | 0.9589 | pathogenic | -1.457 | Destabilizing | 0.993 | D | 0.713 | prob.delet. | None | None | None | None | I |
| V/R | 0.9477 | likely_pathogenic | 0.964 | pathogenic | -0.893 | Destabilizing | 0.993 | D | 0.733 | prob.delet. | None | None | None | None | I |
| V/S | 0.8716 | likely_pathogenic | 0.8843 | pathogenic | -1.799 | Destabilizing | 0.973 | D | 0.673 | neutral | None | None | None | None | I |
| V/T | 0.764 | likely_pathogenic | 0.7328 | pathogenic | -1.673 | Destabilizing | 0.953 | D | 0.575 | neutral | None | None | None | None | I |
| V/W | 0.9906 | likely_pathogenic | 0.9975 | pathogenic | -1.571 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| V/Y | 0.9592 | likely_pathogenic | 0.9831 | pathogenic | -1.279 | Destabilizing | 0.998 | D | 0.679 | prob.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.