Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31126 | 93601;93602;93603 | chr2:178548250;178548249;178548248 | chr2:179412977;179412976;179412975 |
| N2AB | 29485 | 88678;88679;88680 | chr2:178548250;178548249;178548248 | chr2:179412977;179412976;179412975 |
| N2A | 28558 | 85897;85898;85899 | chr2:178548250;178548249;178548248 | chr2:179412977;179412976;179412975 |
| N2B | 22061 | 66406;66407;66408 | chr2:178548250;178548249;178548248 | chr2:179412977;179412976;179412975 |
| Novex-1 | 22186 | 66781;66782;66783 | chr2:178548250;178548249;178548248 | chr2:179412977;179412976;179412975 |
| Novex-2 | 22253 | 66982;66983;66984 | chr2:178548250;178548249;178548248 | chr2:179412977;179412976;179412975 |
| 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/C | None | None | 0.995 | N | 0.476 | 0.489 | 0.430010490656 | gnomAD-4.0.0 | 6.84181E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51915E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | None | None | 0.722 | N | 0.412 | 0.214 | 0.252162846088 | gnomAD-4.0.0 | 6.84181E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65645E-05 |
| S/R | None | None | 0.901 | N | 0.449 | 0.286 | 0.294206760003 | gnomAD-4.0.0 | 1.59112E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85794E-06 | 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 | 0.1532 | likely_benign | 0.1583 | benign | -0.637 | Destabilizing | 0.415 | N | 0.403 | neutral | None | None | None | None | N |
| S/C | 0.1812 | likely_benign | 0.177 | benign | -0.608 | Destabilizing | 0.995 | D | 0.476 | neutral | N | 0.506784508 | None | None | N |
| S/D | 0.4483 | ambiguous | 0.4017 | ambiguous | -0.902 | Destabilizing | 0.775 | D | 0.428 | neutral | None | None | None | None | N |
| S/E | 0.7393 | likely_pathogenic | 0.7012 | pathogenic | -0.926 | Destabilizing | 0.775 | D | 0.417 | neutral | None | None | None | None | N |
| S/F | 0.5396 | ambiguous | 0.5608 | ambiguous | -1.003 | Destabilizing | 0.961 | D | 0.539 | neutral | None | None | None | None | N |
| S/G | 0.0861 | likely_benign | 0.0814 | benign | -0.841 | Destabilizing | 0.722 | D | 0.412 | neutral | N | 0.474613381 | None | None | N |
| S/H | 0.5534 | ambiguous | 0.5386 | ambiguous | -1.378 | Destabilizing | 0.996 | D | 0.477 | neutral | None | None | None | None | N |
| S/I | 0.5927 | likely_pathogenic | 0.6161 | pathogenic | -0.209 | Destabilizing | 0.82 | D | 0.465 | neutral | N | 0.488680253 | None | None | N |
| S/K | 0.8177 | likely_pathogenic | 0.7908 | pathogenic | -0.774 | Destabilizing | 0.775 | D | 0.422 | neutral | None | None | None | None | N |
| S/L | 0.2156 | likely_benign | 0.2288 | benign | -0.209 | Destabilizing | 0.633 | D | 0.433 | neutral | None | None | None | None | N |
| S/M | 0.3512 | ambiguous | 0.3648 | ambiguous | 0.2 | Stabilizing | 0.989 | D | 0.479 | neutral | None | None | None | None | N |
| S/N | 0.1984 | likely_benign | 0.1981 | benign | -0.809 | Destabilizing | 0.722 | D | 0.452 | neutral | N | 0.498394318 | None | None | N |
| S/P | 0.9122 | likely_pathogenic | 0.8966 | pathogenic | -0.32 | Destabilizing | 0.961 | D | 0.453 | neutral | None | None | None | None | N |
| S/Q | 0.6896 | likely_pathogenic | 0.6743 | pathogenic | -1.095 | Destabilizing | 0.961 | D | 0.455 | neutral | None | None | None | None | N |
| S/R | 0.7636 | likely_pathogenic | 0.7351 | pathogenic | -0.533 | Destabilizing | 0.901 | D | 0.449 | neutral | N | 0.495836802 | None | None | N |
| S/T | 0.0705 | likely_benign | 0.0716 | benign | -0.768 | Destabilizing | 0.001 | N | 0.11 | neutral | N | 0.38606889 | None | None | N |
| S/V | 0.484 | ambiguous | 0.4958 | ambiguous | -0.32 | Destabilizing | 0.633 | D | 0.44 | neutral | None | None | None | None | N |
| S/W | 0.6591 | likely_pathogenic | 0.6427 | pathogenic | -0.987 | Destabilizing | 0.996 | D | 0.589 | neutral | None | None | None | None | N |
| S/Y | 0.4344 | ambiguous | 0.4379 | ambiguous | -0.698 | Destabilizing | 0.961 | D | 0.541 | 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.