Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33743 | 101452;101453;101454 | chr2:178535388;178535387;178535386 | chr2:179400115;179400114;179400113 |
| N2AB | 32102 | 96529;96530;96531 | chr2:178535388;178535387;178535386 | chr2:179400115;179400114;179400113 |
| N2A | 31175 | 93748;93749;93750 | chr2:178535388;178535387;178535386 | chr2:179400115;179400114;179400113 |
| N2B | 24678 | 74257;74258;74259 | chr2:178535388;178535387;178535386 | chr2:179400115;179400114;179400113 |
| Novex-1 | 24803 | 74632;74633;74634 | chr2:178535388;178535387;178535386 | chr2:179400115;179400114;179400113 |
| Novex-2 | 24870 | 74833;74834;74835 | chr2:178535388;178535387;178535386 | chr2:179400115;179400114;179400113 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.901 | N | 0.525 | 0.272 | 0.483374165343 | gnomAD-4.0.0 | 6.84183E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99425E-07 | 0 | 0 |
| R/Q | rs746547856  |
0.259 | 0.996 | N | 0.537 | 0.274 | 0.17258766438 | gnomAD-2.1.1 | 7.13E-06 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs746547856 |
0.259 | 0.996 | N | 0.537 | 0.274 | 0.17258766438 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.92382E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs746547856 |
0.259 | 0.996 | N | 0.537 | 0.274 | 0.17258766438 | gnomAD-4.0.0 | 1.1154E-05 | None | None | None | None | N | None | 1.33486E-05 | 0 | None | 0 | 4.45474E-05 | None | 0 | 0 | 1.01708E-05 | 0 | 4.80292E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3994 | ambiguous | 0.4999 | ambiguous | -0.042 | Destabilizing | 0.704 | D | 0.492 | neutral | None | None | None | None | N |
| R/C | 0.3118 | likely_benign | 0.3863 | ambiguous | -0.11 | Destabilizing | 0.999 | D | 0.446 | neutral | None | None | None | None | N |
| R/D | 0.7152 | likely_pathogenic | 0.7878 | pathogenic | -0.098 | Destabilizing | 0.92 | D | 0.475 | neutral | None | None | None | None | N |
| R/E | 0.4199 | ambiguous | 0.5012 | ambiguous | -0.046 | Destabilizing | 0.775 | D | 0.531 | neutral | None | None | None | None | N |
| R/F | 0.7262 | likely_pathogenic | 0.8295 | pathogenic | -0.293 | Destabilizing | 0.99 | D | 0.455 | neutral | None | None | None | None | N |
| R/G | 0.2585 | likely_benign | 0.3375 | benign | -0.223 | Destabilizing | 0.957 | D | 0.525 | neutral | N | 0.511880903 | None | None | N |
| R/H | 0.1833 | likely_benign | 0.2073 | benign | -0.692 | Destabilizing | 0.99 | D | 0.526 | neutral | None | None | None | None | N |
| R/I | 0.4608 | ambiguous | 0.6053 | pathogenic | 0.397 | Stabilizing | 0.944 | D | 0.468 | neutral | None | None | None | None | N |
| R/K | 0.1232 | likely_benign | 0.1236 | benign | -0.072 | Destabilizing | 0.362 | N | 0.481 | neutral | None | None | None | None | N |
| R/L | 0.3736 | ambiguous | 0.4611 | ambiguous | 0.397 | Stabilizing | 0.901 | D | 0.525 | neutral | N | 0.462879022 | None | None | N |
| R/M | 0.4271 | ambiguous | 0.546 | ambiguous | 0.063 | Stabilizing | 0.997 | D | 0.492 | neutral | None | None | None | None | N |
| R/N | 0.6064 | likely_pathogenic | 0.6916 | pathogenic | 0.219 | Stabilizing | 0.92 | D | 0.536 | neutral | None | None | None | None | N |
| R/P | 0.4728 | ambiguous | 0.5932 | pathogenic | 0.27 | Stabilizing | 0.998 | D | 0.474 | neutral | N | 0.414239713 | None | None | N |
| R/Q | 0.1394 | likely_benign | 0.1462 | benign | 0.077 | Stabilizing | 0.996 | D | 0.537 | neutral | N | 0.473096016 | None | None | N |
| R/S | 0.4759 | ambiguous | 0.578 | pathogenic | -0.144 | Destabilizing | 0.309 | N | 0.311 | neutral | None | None | None | None | N |
| R/T | 0.2821 | likely_benign | 0.3656 | ambiguous | 0.032 | Stabilizing | 0.061 | N | 0.235 | neutral | None | None | None | None | N |
| R/V | 0.4849 | ambiguous | 0.6012 | pathogenic | 0.27 | Stabilizing | 0.775 | D | 0.47 | neutral | None | None | None | None | N |
| R/W | 0.337 | likely_benign | 0.4362 | ambiguous | -0.342 | Destabilizing | 0.999 | D | 0.544 | neutral | None | None | None | None | N |
| R/Y | 0.6302 | likely_pathogenic | 0.7303 | pathogenic | 0.063 | Stabilizing | 0.99 | D | 0.476 | 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.