Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1085 | 3478;3479;3480 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
| N2AB | 1085 | 3478;3479;3480 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
| N2A | 1085 | 3478;3479;3480 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
| N2B | 1039 | 3340;3341;3342 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
| Novex-1 | 1039 | 3340;3341;3342 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
| Novex-2 | 1039 | 3340;3341;3342 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
| Novex-3 | 1085 | 3478;3479;3480 | chr2:178782339;178782338;178782337 | chr2:179647066;179647065;179647064 |
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/F | None | None | 0.317 | N | 0.325 | 0.146 | 0.33835085245 | gnomAD-4.0.0 | 6.84076E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.993E-07 | 0 | 0 |
| I/V | rs2092854519  |
None | None | N | 0.131 | 0.056 | 0.262662153117 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2092854519 |
None | None | N | 0.131 | 0.056 | 0.262662153117 | gnomAD-4.0.0 | 4.33709E-06 | None | None | None | None | I | None | 0 | 1.66689E-05 | None | 0 | 0 | None | 0 | 0 | 4.23727E-06 | 0 | 1.60041E-05 |
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 | 0.7573 | likely_pathogenic | 0.743 | pathogenic | -1.214 | Destabilizing | 0.035 | N | 0.35 | neutral | None | None | None | None | I |
| I/C | 0.9052 | likely_pathogenic | 0.8882 | pathogenic | -0.766 | Destabilizing | 0.824 | D | 0.342 | neutral | None | None | None | None | I |
| I/D | 0.9711 | likely_pathogenic | 0.9649 | pathogenic | -0.29 | Destabilizing | 0.555 | D | 0.379 | neutral | None | None | None | None | I |
| I/E | 0.9191 | likely_pathogenic | 0.9132 | pathogenic | -0.293 | Destabilizing | 0.555 | D | 0.372 | neutral | None | None | None | None | I |
| I/F | 0.2665 | likely_benign | 0.2216 | benign | -0.741 | Destabilizing | 0.317 | N | 0.325 | neutral | N | 0.456219242 | None | None | I |
| I/G | 0.9486 | likely_pathogenic | 0.9397 | pathogenic | -1.503 | Destabilizing | 0.555 | D | 0.37 | neutral | None | None | None | None | I |
| I/H | 0.8458 | likely_pathogenic | 0.8299 | pathogenic | -0.529 | Destabilizing | 0.935 | D | 0.345 | neutral | None | None | None | None | I |
| I/K | 0.8116 | likely_pathogenic | 0.8114 | pathogenic | -0.685 | Destabilizing | 0.555 | D | 0.367 | neutral | None | None | None | None | I |
| I/L | 0.1596 | likely_benign | 0.1465 | benign | -0.519 | Destabilizing | None | N | 0.102 | neutral | N | 0.420823121 | None | None | I |
| I/M | 0.1988 | likely_benign | 0.1801 | benign | -0.488 | Destabilizing | 0.012 | N | 0.201 | neutral | N | 0.456515098 | None | None | I |
| I/N | 0.7841 | likely_pathogenic | 0.7775 | pathogenic | -0.576 | Destabilizing | 0.741 | D | 0.368 | neutral | N | 0.453785179 | None | None | I |
| I/P | 0.9592 | likely_pathogenic | 0.9509 | pathogenic | -0.718 | Destabilizing | 0.791 | D | 0.377 | neutral | None | None | None | None | I |
| I/Q | 0.8166 | likely_pathogenic | 0.8073 | pathogenic | -0.719 | Destabilizing | 0.555 | D | 0.365 | neutral | None | None | None | None | I |
| I/R | 0.7339 | likely_pathogenic | 0.7296 | pathogenic | -0.118 | Destabilizing | 0.555 | D | 0.381 | neutral | None | None | None | None | I |
| I/S | 0.758 | likely_pathogenic | 0.7473 | pathogenic | -1.215 | Destabilizing | 0.117 | N | 0.342 | neutral | N | 0.44439247 | None | None | I |
| I/T | 0.6524 | likely_pathogenic | 0.6504 | pathogenic | -1.099 | Destabilizing | 0.062 | N | 0.357 | neutral | N | 0.422456795 | None | None | I |
| I/V | 0.119 | likely_benign | 0.1168 | benign | -0.718 | Destabilizing | None | N | 0.131 | neutral | N | 0.381021504 | None | None | I |
| I/W | 0.9152 | likely_pathogenic | 0.8901 | pathogenic | -0.776 | Destabilizing | 0.935 | D | 0.399 | neutral | None | None | None | None | I |
| I/Y | 0.7729 | likely_pathogenic | 0.7392 | pathogenic | -0.548 | Destabilizing | 0.555 | D | 0.37 | 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.