Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4765 | 14518;14519;14520 | chr2:178738160;178738159;178738158 | chr2:179602887;179602886;179602885 |
| N2AB | 4448 | 13567;13568;13569 | chr2:178738160;178738159;178738158 | chr2:179602887;179602886;179602885 |
| N2A | 3521 | 10786;10787;10788 | chr2:178738160;178738159;178738158 | chr2:179602887;179602886;179602885 |
| N2B | 4402 | 13429;13430;13431 | chr2:178738160;178738159;178738158 | chr2:179602887;179602886;179602885 |
| Novex-1 | 4527 | 13804;13805;13806 | chr2:178738160;178738159;178738158 | chr2:179602887;179602886;179602885 |
| Novex-2 | 4594 | 14005;14006;14007 | chr2:178738160;178738159;178738158 | chr2:179602887;179602886;179602885 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1192234880  |
0.077 | 0.002 | N | 0.094 | 0.092 | 0.167679373172 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1192234880 |
0.077 | 0.002 | N | 0.094 | 0.092 | 0.167679373172 | gnomAD-4.0.0 | 5.4738E-06 | None | None | None | None | I | None | 0 | 2.23624E-05 | None | 0 | 0 | None | 0 | 0 | 5.39688E-06 | 1.15937E-05 | 0 |
| V/D | rs1192234880 |
None | 0.669 | N | 0.367 | 0.189 | 0.468917363747 | gnomAD-4.0.0 | 1.36845E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79896E-06 | 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 | 0.2749 | likely_benign | 0.3473 | ambiguous | -0.388 | Destabilizing | 0.002 | N | 0.094 | neutral | N | 0.38281567 | None | None | I |
| V/C | 0.9113 | likely_pathogenic | 0.9425 | pathogenic | -0.553 | Destabilizing | 0.993 | D | 0.329 | neutral | None | None | None | None | I |
| V/D | 0.7201 | likely_pathogenic | 0.7686 | pathogenic | -0.38 | Destabilizing | 0.669 | D | 0.367 | neutral | N | 0.41059304 | None | None | I |
| V/E | 0.6123 | likely_pathogenic | 0.6415 | pathogenic | -0.505 | Destabilizing | 0.067 | N | 0.203 | neutral | None | None | None | None | I |
| V/F | 0.3511 | ambiguous | 0.4577 | ambiguous | -0.694 | Destabilizing | 0.966 | D | 0.35 | neutral | N | 0.414562129 | None | None | I |
| V/G | 0.4177 | ambiguous | 0.5067 | ambiguous | -0.499 | Destabilizing | 0.454 | N | 0.343 | neutral | N | 0.41238533 | None | None | I |
| V/H | 0.8729 | likely_pathogenic | 0.9083 | pathogenic | -0.059 | Destabilizing | 0.998 | D | 0.343 | neutral | None | None | None | None | I |
| V/I | 0.0955 | likely_benign | 0.1163 | benign | -0.247 | Destabilizing | 0.625 | D | 0.274 | neutral | N | 0.384675865 | None | None | I |
| V/K | 0.7548 | likely_pathogenic | 0.7906 | pathogenic | -0.381 | Destabilizing | 0.842 | D | 0.359 | neutral | None | None | None | None | I |
| V/L | 0.3979 | ambiguous | 0.529 | ambiguous | -0.247 | Destabilizing | 0.625 | D | 0.332 | neutral | N | 0.41407829 | None | None | I |
| V/M | 0.2748 | likely_benign | 0.3735 | ambiguous | -0.293 | Destabilizing | 0.991 | D | 0.345 | neutral | None | None | None | None | I |
| V/N | 0.5891 | likely_pathogenic | 0.6821 | pathogenic | -0.093 | Destabilizing | 0.949 | D | 0.384 | neutral | None | None | None | None | I |
| V/P | 0.7589 | likely_pathogenic | 0.7989 | pathogenic | -0.26 | Destabilizing | 0.974 | D | 0.371 | neutral | None | None | None | None | I |
| V/Q | 0.6617 | likely_pathogenic | 0.7287 | pathogenic | -0.363 | Destabilizing | 0.949 | D | 0.377 | neutral | None | None | None | None | I |
| V/R | 0.6854 | likely_pathogenic | 0.7102 | pathogenic | 0.173 | Stabilizing | 0.949 | D | 0.385 | neutral | None | None | None | None | I |
| V/S | 0.3562 | ambiguous | 0.4478 | ambiguous | -0.422 | Destabilizing | 0.172 | N | 0.237 | neutral | None | None | None | None | I |
| V/T | 0.2857 | likely_benign | 0.3379 | benign | -0.451 | Destabilizing | 0.525 | D | 0.225 | neutral | None | None | None | None | I |
| V/W | 0.9267 | likely_pathogenic | 0.9482 | pathogenic | -0.765 | Destabilizing | 0.998 | D | 0.4 | neutral | None | None | None | None | I |
| V/Y | 0.8334 | likely_pathogenic | 0.8737 | pathogenic | -0.465 | Destabilizing | 0.991 | D | 0.351 | 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.