Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33011 | 99256;99257;99258 | chr2:178538798;178538797;178538796 | chr2:179403525;179403524;179403523 |
| N2AB | 31370 | 94333;94334;94335 | chr2:178538798;178538797;178538796 | chr2:179403525;179403524;179403523 |
| N2A | 30443 | 91552;91553;91554 | chr2:178538798;178538797;178538796 | chr2:179403525;179403524;179403523 |
| N2B | 23946 | 72061;72062;72063 | chr2:178538798;178538797;178538796 | chr2:179403525;179403524;179403523 |
| Novex-1 | 24071 | 72436;72437;72438 | chr2:178538798;178538797;178538796 | chr2:179403525;179403524;179403523 |
| Novex-2 | 24138 | 72637;72638;72639 | chr2:178538798;178538797;178538796 | chr2:179403525;179403524;179403523 |
| 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/T | rs78814506  |
-0.856 | 0.007 | N | 0.081 | 0.098 | None | gnomAD-2.1.1 | 8.76109E-04 | None | None | None | None | N | None | 1.24131E-04 | 8.54E-05 | None | 3.90854E-04 | 1.143E-02 | None | 1.65859E-04 | None | 0 | 7.85E-06 | 7.06814E-04 |
| S/T | rs78814506 |
-0.856 | 0.007 | N | 0.081 | 0.098 | None | gnomAD-3.1.2 | 6.11376E-04 | None | None | None | None | N | None | 4.83E-05 | 1.63784E-03 | 0 | 0 | 1.13812E-02 | None | 0 | 0 | 1.47E-05 | 0 | 2.86807E-03 |
| S/T | rs78814506 |
-0.856 | 0.007 | N | 0.081 | 0.098 | None | 1000 genomes | 2.39617E-03 | None | None | None | None | N | None | 0 | 0 | None | None | 1.19E-02 | 0 | None | None | None | 0 | None |
| S/T | rs78814506 |
-0.856 | 0.007 | N | 0.081 | 0.098 | None | gnomAD-4.0.0 | 3.37505E-04 | None | None | None | None | N | None | 4.00545E-05 | 4.67852E-04 | None | 2.70874E-04 | 6.69016E-03 | None | 0 | 0 | 7.63566E-06 | 6.6139E-05 | 3.04409E-03 |
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 | 0.0967 | likely_benign | 0.1053 | benign | -0.69 | Destabilizing | 0.625 | D | 0.356 | neutral | N | 0.456934485 | None | None | N |
| S/C | 0.132 | likely_benign | 0.1565 | benign | -0.48 | Destabilizing | 0.997 | D | 0.431 | neutral | N | 0.479463542 | None | None | N |
| S/D | 0.5584 | ambiguous | 0.6227 | pathogenic | -0.036 | Destabilizing | 0.915 | D | 0.437 | neutral | None | None | None | None | N |
| S/E | 0.6692 | likely_pathogenic | 0.7385 | pathogenic | -0.089 | Destabilizing | 0.915 | D | 0.42 | neutral | None | None | None | None | N |
| S/F | 0.2536 | likely_benign | 0.4121 | ambiguous | -1.099 | Destabilizing | 0.012 | N | 0.307 | neutral | N | 0.487161391 | None | None | N |
| S/G | 0.1033 | likely_benign | 0.1119 | benign | -0.864 | Destabilizing | 0.915 | D | 0.384 | neutral | None | None | None | None | N |
| S/H | 0.436 | ambiguous | 0.5446 | ambiguous | -1.385 | Destabilizing | 0.991 | D | 0.439 | neutral | None | None | None | None | N |
| S/I | 0.3525 | ambiguous | 0.4348 | ambiguous | -0.347 | Destabilizing | 0.728 | D | 0.424 | neutral | None | None | None | None | N |
| S/K | 0.7915 | likely_pathogenic | 0.8499 | pathogenic | -0.621 | Destabilizing | 0.842 | D | 0.433 | neutral | None | None | None | None | N |
| S/L | 0.1327 | likely_benign | 0.1641 | benign | -0.347 | Destabilizing | 0.525 | D | 0.407 | neutral | None | None | None | None | N |
| S/M | 0.2601 | likely_benign | 0.2996 | benign | 0.032 | Stabilizing | 0.974 | D | 0.449 | neutral | None | None | None | None | N |
| S/N | 0.1741 | likely_benign | 0.2 | benign | -0.456 | Destabilizing | 0.915 | D | 0.467 | neutral | None | None | None | None | N |
| S/P | 0.8607 | likely_pathogenic | 0.9284 | pathogenic | -0.431 | Destabilizing | 0.989 | D | 0.454 | neutral | D | 0.524428913 | None | None | N |
| S/Q | 0.5652 | likely_pathogenic | 0.6431 | pathogenic | -0.714 | Destabilizing | 0.991 | D | 0.461 | neutral | None | None | None | None | N |
| S/R | 0.7205 | likely_pathogenic | 0.8027 | pathogenic | -0.447 | Destabilizing | 0.974 | D | 0.453 | neutral | None | None | None | None | N |
| S/T | 0.083 | likely_benign | 0.0797 | benign | -0.565 | Destabilizing | 0.007 | N | 0.081 | neutral | N | 0.378796201 | None | None | N |
| S/V | 0.306 | likely_benign | 0.3726 | ambiguous | -0.431 | Destabilizing | 0.842 | D | 0.399 | neutral | None | None | None | None | N |
| S/W | 0.508 | ambiguous | 0.6777 | pathogenic | -1.027 | Destabilizing | 0.998 | D | 0.471 | neutral | None | None | None | None | N |
| S/Y | 0.2527 | likely_benign | 0.4121 | ambiguous | -0.776 | Destabilizing | 0.876 | D | 0.451 | neutral | N | 0.499127824 | 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.