Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25264 | 76015;76016;76017 | chr2:178570342;178570341;178570340 | chr2:179435069;179435068;179435067 |
| N2AB | 23623 | 71092;71093;71094 | chr2:178570342;178570341;178570340 | chr2:179435069;179435068;179435067 |
| N2A | 22696 | 68311;68312;68313 | chr2:178570342;178570341;178570340 | chr2:179435069;179435068;179435067 |
| N2B | 16199 | 48820;48821;48822 | chr2:178570342;178570341;178570340 | chr2:179435069;179435068;179435067 |
| Novex-1 | 16324 | 49195;49196;49197 | chr2:178570342;178570341;178570340 | chr2:179435069;179435068;179435067 |
| Novex-2 | 16391 | 49396;49397;49398 | chr2:178570342;178570341;178570340 | chr2:179435069;179435068;179435067 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/S | rs998269154  |
-0.967 | 0.012 | D | 0.442 | 0.242 | 0.476986058749 | 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 |
| C/S | rs998269154 |
-0.967 | 0.012 | D | 0.442 | 0.242 | 0.476986058749 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| C/S | rs998269154 |
-0.967 | 0.012 | D | 0.442 | 0.242 | 0.476986058749 | gnomAD-4.0.0 | 1.31479E-05 | None | None | None | None | N | None | 4.82509E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.4977 | ambiguous | 0.5522 | ambiguous | -1.573 | Destabilizing | None | N | 0.17 | neutral | None | None | None | None | N |
| C/D | 0.9237 | likely_pathogenic | 0.9445 | pathogenic | 0.173 | Stabilizing | 0.072 | N | 0.611 | neutral | None | None | None | None | N |
| C/E | 0.9159 | likely_pathogenic | 0.9385 | pathogenic | 0.296 | Stabilizing | 0.072 | N | 0.571 | neutral | None | None | None | None | N |
| C/F | 0.1827 | likely_benign | 0.2074 | benign | -0.97 | Destabilizing | 0.029 | N | 0.549 | neutral | N | 0.423779129 | None | None | N |
| C/G | 0.3714 | ambiguous | 0.4057 | ambiguous | -1.887 | Destabilizing | 0.012 | N | 0.515 | neutral | N | 0.487738293 | None | None | N |
| C/H | 0.526 | ambiguous | 0.6008 | pathogenic | -1.769 | Destabilizing | None | N | 0.589 | neutral | None | None | None | None | N |
| C/I | 0.4199 | ambiguous | 0.4906 | ambiguous | -0.765 | Destabilizing | 0.016 | N | 0.44 | neutral | None | None | None | None | N |
| C/K | 0.8463 | likely_pathogenic | 0.8907 | pathogenic | -0.525 | Destabilizing | 0.072 | N | 0.573 | neutral | None | None | None | None | N |
| C/L | 0.2989 | likely_benign | 0.3496 | ambiguous | -0.765 | Destabilizing | None | N | 0.363 | neutral | None | None | None | None | N |
| C/M | 0.5269 | ambiguous | 0.5964 | pathogenic | 0.052 | Stabilizing | 0.214 | N | 0.553 | neutral | None | None | None | None | N |
| C/N | 0.727 | likely_pathogenic | 0.7746 | pathogenic | -0.667 | Destabilizing | 0.072 | N | 0.614 | neutral | None | None | None | None | N |
| C/P | 0.9862 | likely_pathogenic | 0.9905 | pathogenic | -1.008 | Destabilizing | 0.356 | N | 0.627 | neutral | None | None | None | None | N |
| C/Q | 0.7217 | likely_pathogenic | 0.7707 | pathogenic | -0.467 | Destabilizing | 0.214 | N | 0.625 | neutral | None | None | None | None | N |
| C/R | 0.5645 | likely_pathogenic | 0.627 | pathogenic | -0.524 | Destabilizing | 0.055 | N | 0.618 | neutral | N | 0.505677964 | None | None | N |
| C/S | 0.4449 | ambiguous | 0.498 | ambiguous | -1.239 | Destabilizing | 0.012 | N | 0.442 | neutral | D | 0.523463334 | None | None | N |
| C/T | 0.5383 | ambiguous | 0.5884 | pathogenic | -0.913 | Destabilizing | 0.031 | N | 0.451 | neutral | None | None | None | None | N |
| C/V | 0.3638 | ambiguous | 0.4299 | ambiguous | -1.008 | Destabilizing | 0.016 | N | 0.487 | neutral | None | None | None | None | N |
| C/W | 0.4685 | ambiguous | 0.5371 | ambiguous | -0.956 | Destabilizing | 0.612 | D | 0.59 | neutral | N | 0.508552597 | None | None | N |
| C/Y | 0.2429 | likely_benign | 0.2884 | benign | -0.915 | Destabilizing | None | N | 0.471 | neutral | N | 0.402323635 | 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.