Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23623 | 71092;71093;71094 | chr2:178575265;178575264;178575263 | chr2:179439992;179439991;179439990 |
| N2AB | 21982 | 66169;66170;66171 | chr2:178575265;178575264;178575263 | chr2:179439992;179439991;179439990 |
| N2A | 21055 | 63388;63389;63390 | chr2:178575265;178575264;178575263 | chr2:179439992;179439991;179439990 |
| N2B | 14558 | 43897;43898;43899 | chr2:178575265;178575264;178575263 | chr2:179439992;179439991;179439990 |
| Novex-1 | 14683 | 44272;44273;44274 | chr2:178575265;178575264;178575263 | chr2:179439992;179439991;179439990 |
| Novex-2 | 14750 | 44473;44474;44475 | chr2:178575265;178575264;178575263 | chr2:179439992;179439991;179439990 |
| 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 | rs1709646432  |
None | None | N | 0.349 | 0.162 | 0.364342057095 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | rs1218196881 |
-0.536 | None | N | 0.085 | 0.085 | 0.237489013734 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/V | rs1218196881 |
-0.536 | None | N | 0.085 | 0.085 | 0.237489013734 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1218196881 |
-0.536 | None | N | 0.085 | 0.085 | 0.237489013734 | gnomAD-4.0.0 | 6.57419E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4708E-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 | 0.1758 | likely_benign | 0.1772 | benign | -1.299 | Destabilizing | 0.024 | N | 0.513 | neutral | None | None | None | None | N |
| I/C | 0.598 | likely_pathogenic | 0.6349 | pathogenic | -0.905 | Destabilizing | 0.764 | D | 0.428 | neutral | None | None | None | None | N |
| I/D | 0.6391 | likely_pathogenic | 0.6501 | pathogenic | -0.697 | Destabilizing | 0.057 | N | 0.513 | neutral | None | None | None | None | N |
| I/E | 0.4465 | ambiguous | 0.45 | ambiguous | -0.691 | Destabilizing | 0.082 | N | 0.521 | neutral | None | None | None | None | N |
| I/F | 0.1577 | likely_benign | 0.1591 | benign | -0.776 | Destabilizing | 0.113 | N | 0.479 | neutral | N | 0.500026327 | None | None | N |
| I/G | 0.5789 | likely_pathogenic | 0.5738 | pathogenic | -1.606 | Destabilizing | 0.057 | N | 0.485 | neutral | None | None | None | None | N |
| I/H | 0.4089 | ambiguous | 0.4267 | ambiguous | -0.68 | Destabilizing | 0.574 | D | 0.457 | neutral | None | None | None | None | N |
| I/K | 0.3004 | likely_benign | 0.302 | benign | -0.93 | Destabilizing | 0.004 | N | 0.515 | neutral | None | None | None | None | N |
| I/L | 0.093 | likely_benign | 0.093 | benign | -0.544 | Destabilizing | None | N | 0.293 | neutral | N | 0.461545297 | None | None | N |
| I/M | 0.081 | likely_benign | 0.0831 | benign | -0.544 | Destabilizing | 0.037 | N | 0.519 | neutral | N | 0.518612088 | None | None | N |
| I/N | 0.2554 | likely_benign | 0.254 | benign | -0.843 | Destabilizing | None | N | 0.455 | neutral | N | 0.481613925 | None | None | N |
| I/P | 0.5651 | likely_pathogenic | 0.5584 | ambiguous | -0.763 | Destabilizing | 0.462 | N | 0.517 | neutral | None | None | None | None | N |
| I/Q | 0.3116 | likely_benign | 0.3203 | benign | -0.981 | Destabilizing | 0.15 | N | 0.535 | neutral | None | None | None | None | N |
| I/R | 0.2189 | likely_benign | 0.2221 | benign | -0.342 | Destabilizing | 0.144 | N | 0.515 | neutral | None | None | None | None | N |
| I/S | 0.211 | likely_benign | 0.2093 | benign | -1.434 | Destabilizing | 0.044 | N | 0.441 | neutral | N | 0.518265371 | None | None | N |
| I/T | 0.0821 | likely_benign | 0.0825 | benign | -1.307 | Destabilizing | None | N | 0.349 | neutral | N | 0.485862164 | None | None | N |
| I/V | 0.0602 | likely_benign | 0.0601 | benign | -0.763 | Destabilizing | None | N | 0.085 | neutral | N | 0.410924475 | None | None | N |
| I/W | 0.7011 | likely_pathogenic | 0.7346 | pathogenic | -0.84 | Destabilizing | 0.936 | D | 0.55 | neutral | None | None | None | None | N |
| I/Y | 0.471 | ambiguous | 0.5057 | ambiguous | -0.616 | Destabilizing | 0.039 | N | 0.502 | 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.