Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15147 | 45664;45665;45666 | chr2:178621279;178621278;178621277 | chr2:179486006;179486005;179486004 |
| N2AB | 13506 | 40741;40742;40743 | chr2:178621279;178621278;178621277 | chr2:179486006;179486005;179486004 |
| N2A | 12579 | 37960;37961;37962 | chr2:178621279;178621278;178621277 | chr2:179486006;179486005;179486004 |
| N2B | 6082 | 18469;18470;18471 | chr2:178621279;178621278;178621277 | chr2:179486006;179486005;179486004 |
| Novex-1 | 6207 | 18844;18845;18846 | chr2:178621279;178621278;178621277 | chr2:179486006;179486005;179486004 |
| Novex-2 | 6274 | 19045;19046;19047 | chr2:178621279;178621278;178621277 | chr2:179486006;179486005;179486004 |
| 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/N | rs369604317  |
0.041 | None | N | 0.131 | 0.126 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/N | rs369604317 |
0.041 | None | N | 0.131 | 0.126 | None | gnomAD-4.0.0 | 5.58282E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63291E-06 | 0 | 0 |
| S/R | rs987487847 |
None | 0.055 | N | 0.464 | 0.229 | 0.319402600006 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs987487847 |
None | 0.055 | N | 0.464 | 0.229 | 0.319402600006 | gnomAD-4.0.0 | 2.03056E-06 | None | None | None | None | N | None | 3.49871E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.0927 | likely_benign | 0.0992 | benign | -0.243 | Destabilizing | None | N | 0.054 | neutral | None | None | None | None | N |
| S/C | 0.2399 | likely_benign | 0.1766 | benign | -0.502 | Destabilizing | 0.295 | N | 0.421 | neutral | N | 0.487569141 | None | None | N |
| S/D | 0.2224 | likely_benign | 0.1685 | benign | 0.277 | Stabilizing | 0.016 | N | 0.325 | neutral | None | None | None | None | N |
| S/E | 0.4128 | ambiguous | 0.3302 | benign | 0.204 | Stabilizing | 0.016 | N | 0.316 | neutral | None | None | None | None | N |
| S/F | 0.281 | likely_benign | 0.3021 | benign | -0.895 | Destabilizing | 0.356 | N | 0.434 | neutral | None | None | None | None | N |
| S/G | 0.0872 | likely_benign | 0.086 | benign | -0.338 | Destabilizing | 0.012 | N | 0.259 | neutral | N | 0.426547369 | None | None | N |
| S/H | 0.3679 | ambiguous | 0.2766 | benign | -0.574 | Destabilizing | 0.214 | N | 0.419 | neutral | None | None | None | None | N |
| S/I | 0.1992 | likely_benign | 0.1655 | benign | -0.122 | Destabilizing | 0.029 | N | 0.329 | neutral | N | 0.501713739 | None | None | N |
| S/K | 0.6158 | likely_pathogenic | 0.4792 | ambiguous | -0.344 | Destabilizing | 0.016 | N | 0.316 | neutral | None | None | None | None | N |
| S/L | 0.1495 | likely_benign | 0.1535 | benign | -0.122 | Destabilizing | 0.016 | N | 0.234 | neutral | None | None | None | None | N |
| S/M | 0.2331 | likely_benign | 0.2286 | benign | -0.305 | Destabilizing | 0.356 | N | 0.413 | neutral | None | None | None | None | N |
| S/N | 0.0818 | likely_benign | 0.0713 | benign | -0.24 | Destabilizing | None | N | 0.131 | neutral | N | 0.396292197 | None | None | N |
| S/P | 0.2937 | likely_benign | 0.2978 | benign | -0.135 | Destabilizing | 0.136 | N | 0.438 | neutral | None | None | None | None | N |
| S/Q | 0.4958 | ambiguous | 0.4136 | ambiguous | -0.38 | Destabilizing | 0.072 | N | 0.433 | neutral | None | None | None | None | N |
| S/R | 0.5758 | likely_pathogenic | 0.4761 | ambiguous | -0.105 | Destabilizing | 0.055 | N | 0.464 | neutral | N | 0.475801443 | None | None | N |
| S/T | 0.0812 | likely_benign | 0.0805 | benign | -0.315 | Destabilizing | None | N | 0.054 | neutral | N | 0.391623714 | None | None | N |
| S/V | 0.2132 | likely_benign | 0.1885 | benign | -0.135 | Destabilizing | None | N | 0.147 | neutral | None | None | None | None | N |
| S/W | 0.4942 | ambiguous | 0.4855 | ambiguous | -0.986 | Destabilizing | 0.864 | D | 0.365 | neutral | None | None | None | None | N |
| S/Y | 0.2301 | likely_benign | 0.2199 | benign | -0.649 | Destabilizing | 0.356 | N | 0.421 | 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.