Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26257 | 78994;78995;78996 | chr2:178567363;178567362;178567361 | chr2:179432090;179432089;179432088 |
| N2AB | 24616 | 74071;74072;74073 | chr2:178567363;178567362;178567361 | chr2:179432090;179432089;179432088 |
| N2A | 23689 | 71290;71291;71292 | chr2:178567363;178567362;178567361 | chr2:179432090;179432089;179432088 |
| N2B | 17192 | 51799;51800;51801 | chr2:178567363;178567362;178567361 | chr2:179432090;179432089;179432088 |
| Novex-1 | 17317 | 52174;52175;52176 | chr2:178567363;178567362;178567361 | chr2:179432090;179432089;179432088 |
| Novex-2 | 17384 | 52375;52376;52377 | chr2:178567363;178567362;178567361 | chr2:179432090;179432089;179432088 |
| 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/V | rs537603440  |
-0.355 | 0.028 | N | 0.205 | 0.188 | 0.432716982437 | gnomAD-2.1.1 | 5.65E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.55902E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs537603440 |
-0.355 | 0.028 | N | 0.205 | 0.188 | 0.432716982437 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.8625E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs537603440 |
-0.355 | 0.028 | N | 0.205 | 0.188 | 0.432716982437 | 1000 genomes | None | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/V | rs537603440 |
-0.355 | 0.028 | N | 0.205 | 0.188 | 0.432716982437 | gnomAD-4.0.0 | 1.12817E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.67893E-04 | None | 0 | 0 | 5.11375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3654 | ambiguous | 0.257 | benign | -1.394 | Destabilizing | 0.373 | N | 0.323 | neutral | None | None | None | None | I |
| I/C | 0.6843 | likely_pathogenic | 0.6098 | pathogenic | -0.765 | Destabilizing | 0.996 | D | 0.38 | neutral | None | None | None | None | I |
| I/D | 0.7767 | likely_pathogenic | 0.6658 | pathogenic | -0.799 | Destabilizing | 0.91 | D | 0.433 | neutral | None | None | None | None | I |
| I/E | 0.6333 | likely_pathogenic | 0.5222 | ambiguous | -0.843 | Destabilizing | 0.59 | D | 0.406 | neutral | None | None | None | None | I |
| I/F | 0.2809 | likely_benign | 0.2112 | benign | -1.099 | Destabilizing | 0.939 | D | 0.366 | neutral | N | 0.475125961 | None | None | I |
| I/G | 0.6375 | likely_pathogenic | 0.514 | ambiguous | -1.662 | Destabilizing | 0.91 | D | 0.405 | neutral | None | None | None | None | I |
| I/H | 0.6347 | likely_pathogenic | 0.5206 | ambiguous | -0.844 | Destabilizing | 0.987 | D | 0.453 | neutral | None | None | None | None | I |
| I/K | 0.4187 | ambiguous | 0.3269 | benign | -0.894 | Destabilizing | 0.009 | N | 0.35 | neutral | None | None | None | None | I |
| I/L | 0.1233 | likely_benign | 0.101 | benign | -0.76 | Destabilizing | 0.309 | N | 0.371 | neutral | N | 0.46344753 | None | None | I |
| I/M | 0.1299 | likely_benign | 0.1055 | benign | -0.5 | Destabilizing | 0.939 | D | 0.392 | neutral | N | 0.486516391 | None | None | I |
| I/N | 0.3388 | likely_benign | 0.2427 | benign | -0.655 | Destabilizing | 0.884 | D | 0.439 | neutral | N | 0.467890558 | None | None | I |
| I/P | 0.9272 | likely_pathogenic | 0.8896 | pathogenic | -0.938 | Destabilizing | 0.953 | D | 0.441 | neutral | None | None | None | None | I |
| I/Q | 0.4893 | ambiguous | 0.374 | ambiguous | -0.888 | Destabilizing | 0.91 | D | 0.447 | neutral | None | None | None | None | I |
| I/R | 0.3662 | ambiguous | 0.2847 | benign | -0.234 | Destabilizing | 0.835 | D | 0.44 | neutral | None | None | None | None | I |
| I/S | 0.3023 | likely_benign | 0.2188 | benign | -1.217 | Destabilizing | 0.521 | D | 0.374 | neutral | N | 0.450208874 | None | None | I |
| I/T | 0.2463 | likely_benign | 0.1882 | benign | -1.149 | Destabilizing | 0.028 | N | 0.251 | neutral | N | 0.422022195 | None | None | I |
| I/V | 0.0682 | likely_benign | 0.061 | benign | -0.938 | Destabilizing | 0.028 | N | 0.205 | neutral | N | 0.415771014 | None | None | I |
| I/W | 0.8808 | likely_pathogenic | 0.8456 | pathogenic | -1.127 | Destabilizing | 0.996 | D | 0.599 | neutral | None | None | None | None | I |
| I/Y | 0.6876 | likely_pathogenic | 0.5972 | pathogenic | -0.911 | Destabilizing | 0.984 | D | 0.374 | 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.