Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1889 | 5890;5891;5892 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
| N2AB | 1889 | 5890;5891;5892 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
| N2A | 1889 | 5890;5891;5892 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
| N2B | 1843 | 5752;5753;5754 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
| Novex-1 | 1843 | 5752;5753;5754 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
| Novex-2 | 1843 | 5752;5753;5754 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
| Novex-3 | 1889 | 5890;5891;5892 | chr2:178776199;178776198;178776197 | chr2:179640926;179640925;179640924 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/F | rs141105443  |
-1.021 | 0.934 | N | 0.515 | 0.564 | None | gnomAD-2.1.1 | 4.6E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.00938E-04 | 0 |
| V/F | rs141105443 |
-1.021 | 0.934 | N | 0.515 | 0.564 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02872E-04 | 0 | 0 |
| V/F | rs141105443 |
-1.021 | 0.934 | N | 0.515 | 0.564 | None | gnomAD-4.0.0 | 1.20814E-04 | None | None | None | None | I | None | 1.33469E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.5593E-04 | 0 | 1.60036E-04 |
| V/I | None | None | 0.267 | N | 0.335 | 0.294 | 0.406806705197 | gnomAD-4.0.0 | 6.8407E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99306E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.568 | likely_pathogenic | 0.5719 | pathogenic | -1.689 | Destabilizing | 0.625 | D | 0.347 | neutral | N | 0.517883036 | None | None | I |
| V/C | 0.8765 | likely_pathogenic | 0.8936 | pathogenic | -1.117 | Destabilizing | 0.998 | D | 0.505 | neutral | None | None | None | None | I |
| V/D | 0.9417 | likely_pathogenic | 0.9393 | pathogenic | -1.543 | Destabilizing | 0.989 | D | 0.603 | neutral | D | 0.632782253 | None | None | I |
| V/E | 0.8114 | likely_pathogenic | 0.8043 | pathogenic | -1.511 | Destabilizing | 0.991 | D | 0.569 | neutral | None | None | None | None | I |
| V/F | 0.3903 | ambiguous | 0.3913 | ambiguous | -1.193 | Destabilizing | 0.934 | D | 0.515 | neutral | N | 0.520689575 | None | None | I |
| V/G | 0.6328 | likely_pathogenic | 0.6386 | pathogenic | -2.055 | Highly Destabilizing | 0.989 | D | 0.591 | neutral | D | 0.671609022 | None | None | I |
| V/H | 0.9098 | likely_pathogenic | 0.9138 | pathogenic | -1.566 | Destabilizing | 0.998 | D | 0.599 | neutral | None | None | None | None | I |
| V/I | 0.0754 | likely_benign | 0.0742 | benign | -0.76 | Destabilizing | 0.267 | N | 0.335 | neutral | N | 0.428945327 | None | None | I |
| V/K | 0.8814 | likely_pathogenic | 0.8809 | pathogenic | -1.462 | Destabilizing | 0.974 | D | 0.549 | neutral | None | None | None | None | I |
| V/L | 0.1356 | likely_benign | 0.1383 | benign | -0.76 | Destabilizing | 0.002 | N | 0.113 | neutral | N | 0.452906865 | None | None | I |
| V/M | 0.1957 | likely_benign | 0.1933 | benign | -0.561 | Destabilizing | 0.949 | D | 0.483 | neutral | None | None | None | None | I |
| V/N | 0.7191 | likely_pathogenic | 0.7259 | pathogenic | -1.263 | Destabilizing | 0.991 | D | 0.601 | neutral | None | None | None | None | I |
| V/P | 0.9092 | likely_pathogenic | 0.9019 | pathogenic | -1.036 | Destabilizing | 0.991 | D | 0.571 | neutral | None | None | None | None | I |
| V/Q | 0.7129 | likely_pathogenic | 0.7193 | pathogenic | -1.393 | Destabilizing | 0.991 | D | 0.572 | neutral | None | None | None | None | I |
| V/R | 0.8765 | likely_pathogenic | 0.88 | pathogenic | -0.942 | Destabilizing | 0.974 | D | 0.601 | neutral | None | None | None | None | I |
| V/S | 0.6549 | likely_pathogenic | 0.6672 | pathogenic | -1.83 | Destabilizing | 0.915 | D | 0.529 | neutral | None | None | None | None | I |
| V/T | 0.5034 | ambiguous | 0.5118 | ambiguous | -1.683 | Destabilizing | 0.915 | D | 0.389 | neutral | None | None | None | None | I |
| V/W | 0.9393 | likely_pathogenic | 0.9419 | pathogenic | -1.42 | Destabilizing | 0.998 | D | 0.616 | neutral | None | None | None | None | I |
| V/Y | 0.84 | likely_pathogenic | 0.8468 | pathogenic | -1.144 | Destabilizing | 0.974 | D | 0.515 | 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.