Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7791 | 23596;23597;23598 | chr2:178720391;178720390;178720389 | chr2:179585118;179585117;179585116 |
| N2AB | 7474 | 22645;22646;22647 | chr2:178720391;178720390;178720389 | chr2:179585118;179585117;179585116 |
| N2A | 6547 | 19864;19865;19866 | chr2:178720391;178720390;178720389 | chr2:179585118;179585117;179585116 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | None | None | 0.999 | N | 0.201 | 0.461 | 0.544825121038 | gnomAD-4.0.0 | 6.85453E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0058E-07 | 0 | 0 |
| F/L | rs727505045  |
-0.732 | 0.005 | N | 0.095 | 0.162 | 0.12205267543 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs727505045 |
-0.732 | 0.005 | N | 0.095 | 0.162 | 0.12205267543 | gnomAD-4.0.0 | 1.37085E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52029E-05 | None | 0 | 0 | 9.0056E-07 | 0 | 0 |
| F/S | rs755115857 |
-1.645 | 0.959 | N | 0.317 | 0.4 | 0.552698843619 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| F/S | rs755115857 |
-1.645 | 0.959 | N | 0.317 | 0.4 | 0.552698843619 | gnomAD-4.0.0 | 4.79817E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30406E-06 | 0 | 0 |
| F/V | None | None | 0.061 | N | 0.145 | 0.158 | 0.239901079897 | gnomAD-4.0.0 | 6.85427E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0056E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.6322 | likely_pathogenic | 0.7334 | pathogenic | -2.025 | Highly Destabilizing | 0.863 | D | 0.282 | neutral | None | None | None | None | I |
| F/C | 0.3869 | ambiguous | 0.4522 | ambiguous | -1.024 | Destabilizing | 0.999 | D | 0.201 | neutral | N | 0.483605719 | None | None | I |
| F/D | 0.8606 | likely_pathogenic | 0.9071 | pathogenic | -0.526 | Destabilizing | 0.997 | D | 0.283 | neutral | None | None | None | None | I |
| F/E | 0.8405 | likely_pathogenic | 0.8876 | pathogenic | -0.435 | Destabilizing | 0.997 | D | 0.295 | neutral | None | None | None | None | I |
| F/G | 0.7968 | likely_pathogenic | 0.8639 | pathogenic | -2.358 | Highly Destabilizing | 0.99 | D | 0.297 | neutral | None | None | None | None | I |
| F/H | 0.7103 | likely_pathogenic | 0.7759 | pathogenic | -0.534 | Destabilizing | 0.999 | D | 0.205 | neutral | None | None | None | None | I |
| F/I | 0.1686 | likely_benign | 0.2067 | benign | -1.032 | Destabilizing | 0.061 | N | 0.121 | neutral | N | 0.403563281 | None | None | I |
| F/K | 0.8864 | likely_pathogenic | 0.9231 | pathogenic | -1.141 | Destabilizing | 0.997 | D | 0.293 | neutral | None | None | None | None | I |
| F/L | 0.6097 | likely_pathogenic | 0.6848 | pathogenic | -1.032 | Destabilizing | 0.005 | N | 0.095 | neutral | N | 0.378150335 | None | None | I |
| F/M | 0.4059 | ambiguous | 0.4606 | ambiguous | -0.769 | Destabilizing | 0.982 | D | 0.233 | neutral | None | None | None | None | I |
| F/N | 0.6806 | likely_pathogenic | 0.7602 | pathogenic | -1.228 | Destabilizing | 0.997 | D | 0.253 | neutral | None | None | None | None | I |
| F/P | 0.8957 | likely_pathogenic | 0.9369 | pathogenic | -1.356 | Destabilizing | 0.997 | D | 0.251 | neutral | None | None | None | None | I |
| F/Q | 0.7622 | likely_pathogenic | 0.8265 | pathogenic | -1.259 | Destabilizing | 0.997 | D | 0.23 | neutral | None | None | None | None | I |
| F/R | 0.8071 | likely_pathogenic | 0.8644 | pathogenic | -0.521 | Destabilizing | 0.997 | D | 0.256 | neutral | None | None | None | None | I |
| F/S | 0.5696 | likely_pathogenic | 0.6757 | pathogenic | -2.041 | Highly Destabilizing | 0.959 | D | 0.317 | neutral | N | 0.483779077 | None | None | I |
| F/T | 0.6327 | likely_pathogenic | 0.7343 | pathogenic | -1.858 | Destabilizing | 0.939 | D | 0.318 | neutral | None | None | None | None | I |
| F/V | 0.2073 | likely_benign | 0.2603 | benign | -1.356 | Destabilizing | 0.061 | N | 0.145 | neutral | N | 0.311903047 | None | None | I |
| F/W | 0.4616 | ambiguous | 0.521 | ambiguous | -0.133 | Destabilizing | 0.999 | D | 0.273 | neutral | None | None | None | None | I |
| F/Y | 0.154 | likely_benign | 0.1762 | benign | -0.383 | Destabilizing | 0.986 | D | 0.275 | neutral | N | 0.483779077 | 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.