Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26709 | 80350;80351;80352 | chr2:178566007;178566006;178566005 | chr2:179430734;179430733;179430732 |
| N2AB | 25068 | 75427;75428;75429 | chr2:178566007;178566006;178566005 | chr2:179430734;179430733;179430732 |
| N2A | 24141 | 72646;72647;72648 | chr2:178566007;178566006;178566005 | chr2:179430734;179430733;179430732 |
| N2B | 17644 | 53155;53156;53157 | chr2:178566007;178566006;178566005 | chr2:179430734;179430733;179430732 |
| Novex-1 | 17769 | 53530;53531;53532 | chr2:178566007;178566006;178566005 | chr2:179430734;179430733;179430732 |
| Novex-2 | 17836 | 53731;53732;53733 | chr2:178566007;178566006;178566005 | chr2:179430734;179430733;179430732 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs757763969  |
-0.424 | 0.684 | N | 0.415 | 0.13 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/T | rs757763969 |
-0.424 | 0.684 | N | 0.415 | 0.13 | None | gnomAD-4.0.0 | 1.5055E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.97912E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2449 | likely_benign | 0.3152 | benign | -0.724 | Destabilizing | 0.742 | D | 0.362 | neutral | None | None | None | None | I |
| I/C | 0.5691 | likely_pathogenic | 0.6372 | pathogenic | -0.706 | Destabilizing | 0.996 | D | 0.422 | neutral | None | None | None | None | I |
| I/D | 0.5735 | likely_pathogenic | 0.6492 | pathogenic | -0.09 | Destabilizing | 0.009 | N | 0.303 | neutral | None | None | None | None | I |
| I/E | 0.5966 | likely_pathogenic | 0.6794 | pathogenic | -0.173 | Destabilizing | 0.59 | D | 0.504 | neutral | None | None | None | None | I |
| I/F | 0.1592 | likely_benign | 0.2003 | benign | -0.671 | Destabilizing | 0.979 | D | 0.354 | neutral | N | 0.469087344 | None | None | I |
| I/G | 0.5773 | likely_pathogenic | 0.6453 | pathogenic | -0.9 | Destabilizing | 0.59 | D | 0.5 | neutral | None | None | None | None | I |
| I/H | 0.4018 | ambiguous | 0.4694 | ambiguous | -0.199 | Destabilizing | 0.987 | D | 0.502 | neutral | None | None | None | None | I |
| I/K | 0.5032 | ambiguous | 0.5659 | pathogenic | -0.403 | Destabilizing | 0.91 | D | 0.471 | neutral | None | None | None | None | I |
| I/L | 0.0996 | likely_benign | 0.1118 | benign | -0.379 | Destabilizing | 0.645 | D | 0.341 | neutral | N | 0.450616227 | None | None | I |
| I/M | 0.0957 | likely_benign | 0.1065 | benign | -0.424 | Destabilizing | 0.979 | D | 0.355 | neutral | N | 0.461779544 | None | None | I |
| I/N | 0.1525 | likely_benign | 0.173 | benign | -0.212 | Destabilizing | 0.007 | N | 0.369 | neutral | N | 0.408422888 | None | None | I |
| I/P | 0.854 | likely_pathogenic | 0.8778 | pathogenic | -0.46 | Destabilizing | 0.953 | D | 0.535 | neutral | None | None | None | None | I |
| I/Q | 0.4299 | ambiguous | 0.4988 | ambiguous | -0.422 | Destabilizing | 0.953 | D | 0.533 | neutral | None | None | None | None | I |
| I/R | 0.3767 | ambiguous | 0.4187 | ambiguous | 0.127 | Stabilizing | 0.91 | D | 0.533 | neutral | None | None | None | None | I |
| I/S | 0.1777 | likely_benign | 0.2174 | benign | -0.703 | Destabilizing | 0.521 | D | 0.458 | neutral | N | 0.449365433 | None | None | I |
| I/T | 0.1114 | likely_benign | 0.1526 | benign | -0.674 | Destabilizing | 0.684 | D | 0.415 | neutral | N | 0.490289336 | None | None | I |
| I/V | 0.0833 | likely_benign | 0.092 | benign | -0.46 | Destabilizing | 0.645 | D | 0.337 | neutral | N | 0.473762445 | None | None | I |
| I/W | 0.6688 | likely_pathogenic | 0.7141 | pathogenic | -0.675 | Destabilizing | 0.996 | D | 0.636 | neutral | None | None | None | None | I |
| I/Y | 0.4293 | ambiguous | 0.4865 | ambiguous | -0.434 | Destabilizing | 0.984 | D | 0.393 | 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.