Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17511 | 52756;52757;52758 | chr2:178608352;178608351;178608350 | chr2:179473079;179473078;179473077 |
| N2AB | 15870 | 47833;47834;47835 | chr2:178608352;178608351;178608350 | chr2:179473079;179473078;179473077 |
| N2A | 14943 | 45052;45053;45054 | chr2:178608352;178608351;178608350 | chr2:179473079;179473078;179473077 |
| N2B | 8446 | 25561;25562;25563 | chr2:178608352;178608351;178608350 | chr2:179473079;179473078;179473077 |
| Novex-1 | 8571 | 25936;25937;25938 | chr2:178608352;178608351;178608350 | chr2:179473079;179473078;179473077 |
| Novex-2 | 8638 | 26137;26138;26139 | chr2:178608352;178608351;178608350 | chr2:179473079;179473078;179473077 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs1446269783  |
-0.462 | 0.063 | N | 0.155 | 0.069 | 0.30921473904 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14732E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs1446269783 |
-0.462 | 0.063 | N | 0.155 | 0.069 | 0.30921473904 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1446269783 |
-0.462 | 0.063 | N | 0.155 | 0.069 | 0.30921473904 | gnomAD-4.0.0 | 6.41858E-06 | None | None | None | None | N | None | 1.69405E-05 | 0 | None | 0 | 0 | None | 0 | 2.24719E-04 | 4.79345E-06 | 1.34239E-05 | 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 | 0.5004 | ambiguous | 0.353 | ambiguous | -1.106 | Destabilizing | 0.472 | N | 0.314 | neutral | N | 0.445253267 | None | None | N |
| V/C | 0.8824 | likely_pathogenic | 0.8153 | pathogenic | -0.829 | Destabilizing | 0.996 | D | 0.443 | neutral | None | None | None | None | N |
| V/D | 0.8693 | likely_pathogenic | 0.7137 | pathogenic | -0.796 | Destabilizing | 0.979 | D | 0.568 | neutral | N | 0.494623294 | None | None | N |
| V/E | 0.7026 | likely_pathogenic | 0.5082 | ambiguous | -0.87 | Destabilizing | 0.984 | D | 0.546 | neutral | None | None | None | None | N |
| V/F | 0.4011 | ambiguous | 0.3164 | benign | -1.062 | Destabilizing | 0.884 | D | 0.408 | neutral | N | 0.474397432 | None | None | N |
| V/G | 0.5845 | likely_pathogenic | 0.4084 | ambiguous | -1.333 | Destabilizing | 0.939 | D | 0.537 | neutral | N | 0.442869109 | None | None | N |
| V/H | 0.9075 | likely_pathogenic | 0.8214 | pathogenic | -0.805 | Destabilizing | 0.996 | D | 0.575 | neutral | None | None | None | None | N |
| V/I | 0.074 | likely_benign | 0.0767 | benign | -0.624 | Destabilizing | 0.001 | N | 0.187 | neutral | N | 0.456798412 | None | None | N |
| V/K | 0.6961 | likely_pathogenic | 0.5127 | ambiguous | -0.853 | Destabilizing | 0.953 | D | 0.549 | neutral | None | None | None | None | N |
| V/L | 0.3343 | likely_benign | 0.2791 | benign | -0.624 | Destabilizing | 0.063 | N | 0.155 | neutral | N | 0.475768175 | None | None | N |
| V/M | 0.2361 | likely_benign | 0.1988 | benign | -0.46 | Destabilizing | 0.91 | D | 0.441 | neutral | None | None | None | None | N |
| V/N | 0.7171 | likely_pathogenic | 0.5568 | ambiguous | -0.562 | Destabilizing | 0.984 | D | 0.576 | neutral | None | None | None | None | N |
| V/P | 0.8993 | likely_pathogenic | 0.7593 | pathogenic | -0.749 | Destabilizing | 0.984 | D | 0.557 | neutral | None | None | None | None | N |
| V/Q | 0.6772 | likely_pathogenic | 0.5236 | ambiguous | -0.831 | Destabilizing | 0.984 | D | 0.565 | neutral | None | None | None | None | N |
| V/R | 0.6709 | likely_pathogenic | 0.5083 | ambiguous | -0.261 | Destabilizing | 0.984 | D | 0.576 | neutral | None | None | None | None | N |
| V/S | 0.6472 | likely_pathogenic | 0.4728 | ambiguous | -1.037 | Destabilizing | 0.953 | D | 0.507 | neutral | None | None | None | None | N |
| V/T | 0.472 | ambiguous | 0.3382 | benign | -1.008 | Destabilizing | 0.742 | D | 0.323 | neutral | None | None | None | None | N |
| V/W | 0.9295 | likely_pathogenic | 0.8783 | pathogenic | -1.13 | Destabilizing | 0.996 | D | 0.62 | neutral | None | None | None | None | N |
| V/Y | 0.788 | likely_pathogenic | 0.6825 | pathogenic | -0.855 | Destabilizing | 0.953 | D | 0.448 | 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.