Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21352 | 64279;64280;64281 | chr2:178587157;178587156;178587155 | chr2:179451884;179451883;179451882 |
| N2AB | 19711 | 59356;59357;59358 | chr2:178587157;178587156;178587155 | chr2:179451884;179451883;179451882 |
| N2A | 18784 | 56575;56576;56577 | chr2:178587157;178587156;178587155 | chr2:179451884;179451883;179451882 |
| N2B | 12287 | 37084;37085;37086 | chr2:178587157;178587156;178587155 | chr2:179451884;179451883;179451882 |
| Novex-1 | 12412 | 37459;37460;37461 | chr2:178587157;178587156;178587155 | chr2:179451884;179451883;179451882 |
| Novex-2 | 12479 | 37660;37661;37662 | chr2:178587157;178587156;178587155 | chr2:179451884;179451883;179451882 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs746114626  |
0.117 | 0.055 | N | 0.505 | 0.106 | 0.268660756437 | gnomAD-2.1.1 | 4.42E-05 | None | None | None | None | N | None | 0 | 2.89788E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65563E-04 |
| T/I | rs746114626 |
0.117 | 0.055 | N | 0.505 | 0.106 | 0.268660756437 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs746114626 |
0.117 | 0.055 | N | 0.505 | 0.106 | 0.268660756437 | gnomAD-4.0.0 | 7.43883E-06 | None | None | None | None | N | None | 0 | 1.8345E-04 | None | 0 | 0 | None | 0 | 0 | 8.47859E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0517 | likely_benign | 0.0604 | benign | -1.07 | Destabilizing | None | N | 0.171 | neutral | N | 0.432281182 | None | None | N |
| T/C | 0.1753 | likely_benign | 0.2292 | benign | -0.847 | Destabilizing | 0.356 | N | 0.497 | neutral | None | None | None | None | N |
| T/D | 0.35 | ambiguous | 0.4633 | ambiguous | -1.084 | Destabilizing | 0.031 | N | 0.418 | neutral | None | None | None | None | N |
| T/E | 0.2455 | likely_benign | 0.3244 | benign | -0.989 | Destabilizing | 0.016 | N | 0.437 | neutral | None | None | None | None | N |
| T/F | 0.1914 | likely_benign | 0.2341 | benign | -0.762 | Destabilizing | 0.356 | N | 0.524 | neutral | None | None | None | None | N |
| T/G | 0.1368 | likely_benign | 0.1746 | benign | -1.418 | Destabilizing | 0.016 | N | 0.443 | neutral | None | None | None | None | N |
| T/H | 0.2136 | likely_benign | 0.2505 | benign | -1.603 | Destabilizing | 0.356 | N | 0.524 | neutral | None | None | None | None | N |
| T/I | 0.1084 | likely_benign | 0.1345 | benign | -0.196 | Destabilizing | 0.055 | N | 0.505 | neutral | N | 0.504085353 | None | None | N |
| T/K | 0.1691 | likely_benign | 0.1818 | benign | -0.959 | Destabilizing | 0.012 | N | 0.425 | neutral | N | 0.456043476 | None | None | N |
| T/L | 0.082 | likely_benign | 0.098 | benign | -0.196 | Destabilizing | 0.016 | N | 0.401 | neutral | None | None | None | None | N |
| T/M | 0.0778 | likely_benign | 0.0983 | benign | -0.076 | Destabilizing | 0.356 | N | 0.507 | neutral | None | None | None | None | N |
| T/N | 0.1178 | likely_benign | 0.1494 | benign | -1.199 | Destabilizing | 0.072 | N | 0.333 | neutral | None | None | None | None | N |
| T/P | 0.4658 | ambiguous | 0.5719 | pathogenic | -0.455 | Destabilizing | 0.055 | N | 0.463 | neutral | N | 0.504258711 | None | None | N |
| T/Q | 0.1739 | likely_benign | 0.2022 | benign | -1.217 | Destabilizing | 0.001 | N | 0.309 | neutral | None | None | None | None | N |
| T/R | 0.1408 | likely_benign | 0.1405 | benign | -0.87 | Destabilizing | None | N | 0.314 | neutral | N | 0.466991189 | None | None | N |
| T/S | 0.0826 | likely_benign | 0.0984 | benign | -1.436 | Destabilizing | None | N | 0.205 | neutral | N | 0.343418899 | None | None | N |
| T/V | 0.075 | likely_benign | 0.0922 | benign | -0.455 | Destabilizing | 0.016 | N | 0.304 | neutral | None | None | None | None | N |
| T/W | 0.5392 | ambiguous | 0.6226 | pathogenic | -0.773 | Destabilizing | 0.864 | D | 0.553 | neutral | None | None | None | None | N |
| T/Y | 0.2265 | likely_benign | 0.2813 | benign | -0.507 | Destabilizing | 0.356 | N | 0.525 | 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.