Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33715 | 101368;101369;101370 | chr2:178535472;178535471;178535470 | chr2:179400199;179400198;179400197 |
| N2AB | 32074 | 96445;96446;96447 | chr2:178535472;178535471;178535470 | chr2:179400199;179400198;179400197 |
| N2A | 31147 | 93664;93665;93666 | chr2:178535472;178535471;178535470 | chr2:179400199;179400198;179400197 |
| N2B | 24650 | 74173;74174;74175 | chr2:178535472;178535471;178535470 | chr2:179400199;179400198;179400197 |
| Novex-1 | 24775 | 74548;74549;74550 | chr2:178535472;178535471;178535470 | chr2:179400199;179400198;179400197 |
| Novex-2 | 24842 | 74749;74750;74751 | chr2:178535472;178535471;178535470 | chr2:179400199;179400198;179400197 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs755892166  |
-1.035 | 0.667 | N | 0.47 | 0.169 | 0.404733080969 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| S/F | rs755892166 |
-1.035 | 0.667 | N | 0.47 | 0.169 | 0.404733080969 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/F | rs755892166 |
-1.035 | 0.667 | N | 0.47 | 0.169 | 0.404733080969 | gnomAD-4.0.0 | 1.11533E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44088E-05 | 0 | 1.60041E-05 |
| S/P | None | None | 0.132 | N | 0.418 | 0.179 | 0.128392430309 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0874 | likely_benign | 0.0872 | benign | -0.489 | Destabilizing | 0.001 | N | 0.271 | neutral | N | 0.476213679 | None | None | N |
| S/C | 0.1196 | likely_benign | 0.1151 | benign | -0.251 | Destabilizing | 0.669 | D | 0.34 | neutral | N | 0.519601883 | None | None | N |
| S/D | 0.3697 | ambiguous | 0.3537 | ambiguous | -0.274 | Destabilizing | 0.02 | N | 0.269 | neutral | None | None | None | None | N |
| S/E | 0.5027 | ambiguous | 0.4643 | ambiguous | -0.368 | Destabilizing | 0.054 | N | 0.266 | neutral | None | None | None | None | N |
| S/F | 0.2021 | likely_benign | 0.1832 | benign | -1.118 | Destabilizing | 0.667 | D | 0.47 | neutral | N | 0.461092298 | None | None | N |
| S/G | 0.1252 | likely_benign | 0.1204 | benign | -0.604 | Destabilizing | 0.071 | N | 0.341 | neutral | None | None | None | None | N |
| S/H | 0.2976 | likely_benign | 0.2745 | benign | -1.208 | Destabilizing | 0.726 | D | 0.369 | neutral | None | None | None | None | N |
| S/I | 0.1717 | likely_benign | 0.153 | benign | -0.312 | Destabilizing | 0.157 | N | 0.479 | neutral | None | None | None | None | N |
| S/K | 0.5856 | likely_pathogenic | 0.5257 | ambiguous | -0.603 | Destabilizing | 0.133 | N | 0.269 | neutral | None | None | None | None | N |
| S/L | 0.1234 | likely_benign | 0.1199 | benign | -0.312 | Destabilizing | 0.157 | N | 0.405 | neutral | None | None | None | None | N |
| S/M | 0.1805 | likely_benign | 0.1809 | benign | 0.151 | Stabilizing | 0.726 | D | 0.354 | neutral | None | None | None | None | N |
| S/N | 0.0984 | likely_benign | 0.1013 | benign | -0.356 | Destabilizing | None | N | 0.079 | neutral | None | None | None | None | N |
| S/P | 0.8058 | likely_pathogenic | 0.7905 | pathogenic | -0.343 | Destabilizing | 0.132 | N | 0.418 | neutral | N | 0.480659493 | None | None | N |
| S/Q | 0.4562 | ambiguous | 0.4242 | ambiguous | -0.665 | Destabilizing | 0.431 | N | 0.346 | neutral | None | None | None | None | N |
| S/R | 0.5021 | ambiguous | 0.4267 | ambiguous | -0.35 | Destabilizing | 0.272 | N | 0.414 | neutral | None | None | None | None | N |
| S/T | 0.0717 | likely_benign | 0.0695 | benign | -0.422 | Destabilizing | None | N | 0.055 | neutral | N | 0.462457735 | None | None | N |
| S/V | 0.1652 | likely_benign | 0.1509 | benign | -0.343 | Destabilizing | 0.065 | N | 0.425 | neutral | None | None | None | None | N |
| S/W | 0.4327 | ambiguous | 0.3887 | ambiguous | -1.112 | Destabilizing | 0.968 | D | 0.482 | neutral | None | None | None | None | N |
| S/Y | 0.1926 | likely_benign | 0.1827 | benign | -0.842 | Destabilizing | 0.667 | D | 0.471 | neutral | N | 0.450683303 | 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.