Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20122 | 60589;60590;60591 | chr2:178591361;178591360;178591359 | chr2:179456088;179456087;179456086 |
| N2AB | 18481 | 55666;55667;55668 | chr2:178591361;178591360;178591359 | chr2:179456088;179456087;179456086 |
| N2A | 17554 | 52885;52886;52887 | chr2:178591361;178591360;178591359 | chr2:179456088;179456087;179456086 |
| N2B | 11057 | 33394;33395;33396 | chr2:178591361;178591360;178591359 | chr2:179456088;179456087;179456086 |
| Novex-1 | 11182 | 33769;33770;33771 | chr2:178591361;178591360;178591359 | chr2:179456088;179456087;179456086 |
| Novex-2 | 11249 | 33970;33971;33972 | chr2:178591361;178591360;178591359 | chr2:179456088;179456087;179456086 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs776191153  |
0.128 | 0.021 | N | 0.149 | 0.061 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.48E-05 | 0 |
| D/N | rs776191153 |
0.128 | 0.021 | N | 0.149 | 0.061 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 2.88018E-04 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| D/N | rs776191153 |
0.128 | 0.021 | N | 0.149 | 0.061 | None | gnomAD-4.0.0 | 8.74065E-05 | None | None | None | None | N | None | 2.67158E-05 | 0 | None | 3.38021E-05 | 0 | None | 0 | 0 | 1.16154E-04 | 0 | 1.60185E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1649 | likely_benign | 0.1565 | benign | -0.563 | Destabilizing | 0.201 | N | 0.287 | neutral | N | 0.515411493 | None | None | N |
| D/C | 0.5551 | ambiguous | 0.5112 | ambiguous | -0.133 | Destabilizing | 0.992 | D | 0.305 | neutral | None | None | None | None | N |
| D/E | 0.1791 | likely_benign | 0.1594 | benign | -0.402 | Destabilizing | 0.001 | N | 0.134 | neutral | N | 0.431659533 | None | None | N |
| D/F | 0.6387 | likely_pathogenic | 0.6048 | pathogenic | -0.306 | Destabilizing | 0.972 | D | 0.311 | neutral | None | None | None | None | N |
| D/G | 0.117 | likely_benign | 0.1135 | benign | -0.82 | Destabilizing | 0.201 | N | 0.287 | neutral | N | 0.454552248 | None | None | N |
| D/H | 0.2855 | likely_benign | 0.2646 | benign | -0.324 | Destabilizing | 0.916 | D | 0.244 | neutral | N | 0.515931568 | None | None | N |
| D/I | 0.4637 | ambiguous | 0.4237 | ambiguous | 0.089 | Stabilizing | 0.92 | D | 0.358 | neutral | None | None | None | None | N |
| D/K | 0.3416 | ambiguous | 0.3178 | benign | -0.024 | Destabilizing | 0.25 | N | 0.293 | neutral | None | None | None | None | N |
| D/L | 0.3783 | ambiguous | 0.3593 | ambiguous | 0.089 | Stabilizing | 0.617 | D | 0.394 | neutral | None | None | None | None | N |
| D/M | 0.5365 | ambiguous | 0.4909 | ambiguous | 0.374 | Stabilizing | 0.992 | D | 0.295 | neutral | None | None | None | None | N |
| D/N | 0.0802 | likely_benign | 0.076 | benign | -0.413 | Destabilizing | 0.021 | N | 0.149 | neutral | N | 0.461846367 | None | None | N |
| D/P | 0.748 | likely_pathogenic | 0.7094 | pathogenic | -0.105 | Destabilizing | 0.766 | D | 0.331 | neutral | None | None | None | None | N |
| D/Q | 0.3307 | likely_benign | 0.3029 | benign | -0.325 | Destabilizing | 0.059 | N | 0.153 | neutral | None | None | None | None | N |
| D/R | 0.4027 | ambiguous | 0.3743 | ambiguous | 0.177 | Stabilizing | 0.617 | D | 0.359 | neutral | None | None | None | None | N |
| D/S | 0.0946 | likely_benign | 0.0893 | benign | -0.555 | Destabilizing | 0.25 | N | 0.291 | neutral | None | None | None | None | N |
| D/T | 0.1653 | likely_benign | 0.1477 | benign | -0.346 | Destabilizing | 0.617 | D | 0.279 | neutral | None | None | None | None | N |
| D/V | 0.27 | likely_benign | 0.2528 | benign | -0.105 | Destabilizing | 0.549 | D | 0.385 | neutral | N | 0.476749338 | None | None | N |
| D/W | 0.8785 | likely_pathogenic | 0.8478 | pathogenic | -0.099 | Destabilizing | 0.992 | D | 0.368 | neutral | None | None | None | None | N |
| D/Y | 0.3301 | likely_benign | 0.3157 | benign | -0.065 | Destabilizing | 0.985 | D | 0.328 | neutral | N | 0.488105643 | 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.