Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2841 | 8746;8747;8748 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
| N2AB | 2841 | 8746;8747;8748 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
| N2A | 2841 | 8746;8747;8748 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
| N2B | 2795 | 8608;8609;8610 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
| Novex-1 | 2795 | 8608;8609;8610 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
| Novex-2 | 2795 | 8608;8609;8610 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
| Novex-3 | 2841 | 8746;8747;8748 | chr2:178770180;178770179;178770178 | chr2:179634907;179634906;179634905 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs779603870  |
-0.824 | 0.002 | N | 0.112 | 0.198 | 0.210429274316 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs779603870 |
-0.824 | 0.002 | N | 0.112 | 0.198 | 0.210429274316 | gnomAD-4.0.0 | 1.36812E-06 | None | None | None | None | N | None | 0 | 2.23604E-05 | None | 0 | 0 | None | 0 | 0 | 8.99292E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5988 | likely_pathogenic | 0.6444 | pathogenic | -0.128 | Destabilizing | 0.688 | D | 0.327 | neutral | None | None | None | None | N |
| R/C | 0.2623 | likely_benign | 0.2514 | benign | -0.145 | Destabilizing | 0.998 | D | 0.366 | neutral | None | None | None | None | N |
| R/D | 0.8208 | likely_pathogenic | 0.8505 | pathogenic | 0.011 | Stabilizing | 0.842 | D | 0.383 | neutral | None | None | None | None | N |
| R/E | 0.5433 | ambiguous | 0.5594 | ambiguous | 0.103 | Stabilizing | 0.525 | D | 0.369 | neutral | None | None | None | None | N |
| R/F | 0.6575 | likely_pathogenic | 0.6734 | pathogenic | -0.183 | Destabilizing | 0.991 | D | 0.367 | neutral | None | None | None | None | N |
| R/G | 0.5123 | ambiguous | 0.5422 | ambiguous | -0.38 | Destabilizing | 0.801 | D | 0.369 | neutral | N | 0.503765598 | None | None | N |
| R/H | 0.1234 | likely_benign | 0.1289 | benign | -0.878 | Destabilizing | 0.974 | D | 0.391 | neutral | None | None | None | None | N |
| R/I | 0.3217 | likely_benign | 0.3186 | benign | 0.515 | Stabilizing | 0.966 | D | 0.38 | neutral | N | 0.515763998 | None | None | N |
| R/K | 0.1292 | likely_benign | 0.144 | benign | -0.143 | Destabilizing | 0.002 | N | 0.112 | neutral | N | 0.397080821 | None | None | N |
| R/L | 0.3292 | likely_benign | 0.3332 | benign | 0.515 | Stabilizing | 0.842 | D | 0.369 | neutral | None | None | None | None | N |
| R/M | 0.3635 | ambiguous | 0.395 | ambiguous | 0.08 | Stabilizing | 0.991 | D | 0.356 | neutral | None | None | None | None | N |
| R/N | 0.6894 | likely_pathogenic | 0.7561 | pathogenic | 0.2 | Stabilizing | 0.842 | D | 0.328 | neutral | None | None | None | None | N |
| R/P | 0.9622 | likely_pathogenic | 0.9527 | pathogenic | 0.323 | Stabilizing | 0.974 | D | 0.353 | neutral | None | None | None | None | N |
| R/Q | 0.1291 | likely_benign | 0.1406 | benign | 0.087 | Stabilizing | 0.172 | N | 0.219 | neutral | None | None | None | None | N |
| R/S | 0.6122 | likely_pathogenic | 0.6669 | pathogenic | -0.27 | Destabilizing | 0.801 | D | 0.349 | neutral | N | 0.470557886 | None | None | N |
| R/T | 0.335 | likely_benign | 0.3723 | ambiguous | -0.02 | Destabilizing | 0.801 | D | 0.327 | neutral | N | 0.506730513 | None | None | N |
| R/V | 0.4146 | ambiguous | 0.4393 | ambiguous | 0.323 | Stabilizing | 0.915 | D | 0.363 | neutral | None | None | None | None | N |
| R/W | 0.2928 | likely_benign | 0.2576 | benign | -0.114 | Destabilizing | 0.998 | D | 0.401 | neutral | None | None | None | None | N |
| R/Y | 0.4962 | ambiguous | 0.5065 | ambiguous | 0.265 | Stabilizing | 0.991 | D | 0.371 | 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.