Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2924 | 8995;8996;8997 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
| N2AB | 2924 | 8995;8996;8997 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
| N2A | 2924 | 8995;8996;8997 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
| N2B | 2878 | 8857;8858;8859 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
| Novex-1 | 2878 | 8857;8858;8859 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
| Novex-2 | 2878 | 8857;8858;8859 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
| Novex-3 | 2924 | 8995;8996;8997 | chr2:178769811;178769810;178769809 | chr2:179634538;179634537;179634536 |
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/N | rs745523949  |
-0.033 | 0.994 | D | 0.435 | 0.36 | 0.39162414616 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| S/N | rs745523949 |
-0.033 | 0.994 | D | 0.435 | 0.36 | 0.39162414616 | gnomAD-4.0.0 | 1.16291E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51902E-05 | None | 0 | 0 | 1.43887E-05 | 0 | 0 |
| S/R | rs778525693 |
0.036 | 0.998 | D | 0.535 | 0.693 | 0.483816155017 | 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 |
| S/R | rs778525693 |
0.036 | 0.998 | D | 0.535 | 0.693 | 0.483816155017 | 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 |
| S/R | rs778525693 |
0.036 | 0.998 | D | 0.535 | 0.693 | 0.483816155017 | gnomAD-4.0.0 | 1.59049E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85652E-06 | 0 | 0 |
| S/T | rs745523949 |
None | 0.543 | D | 0.267 | 0.378 | 0.28297238246 | gnomAD-4.0.0 | 6.84062E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.4702 | ambiguous | 0.3943 | ambiguous | -0.427 | Destabilizing | 0.98 | D | 0.351 | neutral | None | None | None | None | N |
| S/C | 0.586 | likely_pathogenic | 0.5421 | ambiguous | -0.326 | Destabilizing | 1.0 | D | 0.541 | neutral | D | 0.66241102 | None | None | N |
| S/D | 0.8284 | likely_pathogenic | 0.8252 | pathogenic | 0.283 | Stabilizing | 0.996 | D | 0.405 | neutral | None | None | None | None | N |
| S/E | 0.9715 | likely_pathogenic | 0.9678 | pathogenic | 0.227 | Stabilizing | 0.996 | D | 0.413 | neutral | None | None | None | None | N |
| S/F | 0.9658 | likely_pathogenic | 0.9506 | pathogenic | -0.887 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| S/G | 0.3547 | ambiguous | 0.3111 | benign | -0.588 | Destabilizing | 0.994 | D | 0.379 | neutral | N | 0.51828671 | None | None | N |
| S/H | 0.924 | likely_pathogenic | 0.9227 | pathogenic | -0.988 | Destabilizing | 1.0 | D | 0.524 | neutral | None | None | None | None | N |
| S/I | 0.9632 | likely_pathogenic | 0.9436 | pathogenic | -0.128 | Destabilizing | 0.997 | D | 0.622 | neutral | D | 0.737554529 | None | None | N |
| S/K | 0.9919 | likely_pathogenic | 0.9913 | pathogenic | -0.484 | Destabilizing | 0.996 | D | 0.404 | neutral | None | None | None | None | N |
| S/L | 0.7665 | likely_pathogenic | 0.6804 | pathogenic | -0.128 | Destabilizing | 0.992 | D | 0.5 | neutral | None | None | None | None | N |
| S/M | 0.8559 | likely_pathogenic | 0.8262 | pathogenic | -0.088 | Destabilizing | 1.0 | D | 0.523 | neutral | None | None | None | None | N |
| S/N | 0.5186 | ambiguous | 0.4822 | ambiguous | -0.288 | Destabilizing | 0.994 | D | 0.435 | neutral | D | 0.528217064 | None | None | N |
| S/P | 0.9895 | likely_pathogenic | 0.9751 | pathogenic | -0.197 | Destabilizing | 1.0 | D | 0.537 | neutral | None | None | None | None | N |
| S/Q | 0.9699 | likely_pathogenic | 0.9693 | pathogenic | -0.43 | Destabilizing | 1.0 | D | 0.49 | neutral | None | None | None | None | N |
| S/R | 0.9881 | likely_pathogenic | 0.9716 | pathogenic | -0.323 | Destabilizing | 0.998 | D | 0.535 | neutral | D | 0.628524127 | None | None | N |
| S/T | 0.2808 | likely_benign | 0.2618 | benign | -0.352 | Destabilizing | 0.543 | D | 0.267 | neutral | D | 0.574811506 | None | None | N |
| S/V | 0.9389 | likely_pathogenic | 0.9127 | pathogenic | -0.197 | Destabilizing | 0.998 | D | 0.56 | neutral | None | None | None | None | N |
| S/W | 0.9642 | likely_pathogenic | 0.9565 | pathogenic | -0.926 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| S/Y | 0.9343 | likely_pathogenic | 0.9144 | pathogenic | -0.634 | Destabilizing | 1.0 | D | 0.613 | 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.