Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14446 | 43561;43562;43563 | chr2:178632670;178632669;178632668 | chr2:179497397;179497396;179497395 |
| N2AB | 12805 | 38638;38639;38640 | chr2:178632670;178632669;178632668 | chr2:179497397;179497396;179497395 |
| N2A | 11878 | 35857;35858;35859 | chr2:178632670;178632669;178632668 | chr2:179497397;179497396;179497395 |
| N2B | 5381 | 16366;16367;16368 | chr2:178632670;178632669;178632668 | chr2:179497397;179497396;179497395 |
| Novex-1 | 5506 | 16741;16742;16743 | chr2:178632670;178632669;178632668 | chr2:179497397;179497396;179497395 |
| Novex-2 | 5573 | 16942;16943;16944 | chr2:178632670;178632669;178632668 | chr2:179497397;179497396;179497395 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/D | rs766663791  |
-0.548 | 0.999 | D | 0.497 | 0.239 | 0.253205268125 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| E/D | rs766663791 |
-0.548 | 0.999 | D | 0.497 | 0.239 | 0.253205268125 | gnomAD-4.0.0 | 7.20193E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.87501E-06 | 0 | 0 |
| E/K | rs774470098 |
0.211 | 0.999 | D | 0.637 | 0.411 | 0.534572409765 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 8.96E-06 | 0 |
| E/K | rs774470098 |
0.211 | 0.999 | D | 0.637 | 0.411 | 0.534572409765 | gnomAD-4.0.0 | 2.73732E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.63768E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2111 | likely_benign | 0.2093 | benign | -0.592 | Destabilizing | 0.999 | D | 0.67 | neutral | D | 0.567560849 | None | None | N |
| E/C | 0.9349 | likely_pathogenic | 0.924 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.652 | neutral | None | None | None | None | N |
| E/D | 0.3183 | likely_benign | 0.3046 | benign | -0.668 | Destabilizing | 0.999 | D | 0.497 | neutral | D | 0.538208368 | None | None | N |
| E/F | 0.8654 | likely_pathogenic | 0.851 | pathogenic | -0.205 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| E/G | 0.3139 | likely_benign | 0.3083 | benign | -0.862 | Destabilizing | 1.0 | D | 0.649 | neutral | D | 0.696573264 | None | None | N |
| E/H | 0.7143 | likely_pathogenic | 0.6979 | pathogenic | -0.118 | Destabilizing | 1.0 | D | 0.622 | neutral | None | None | None | None | N |
| E/I | 0.4265 | ambiguous | 0.4137 | ambiguous | 0.112 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/K | 0.2455 | likely_benign | 0.2453 | benign | -0.009 | Destabilizing | 0.999 | D | 0.637 | neutral | D | 0.552120716 | None | None | N |
| E/L | 0.5101 | ambiguous | 0.4975 | ambiguous | 0.112 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/M | 0.5493 | ambiguous | 0.5244 | ambiguous | 0.235 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| E/N | 0.4664 | ambiguous | 0.4642 | ambiguous | -0.483 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| E/P | 0.5324 | ambiguous | 0.5291 | ambiguous | -0.102 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/Q | 0.2347 | likely_benign | 0.2314 | benign | -0.414 | Destabilizing | 1.0 | D | 0.597 | neutral | D | 0.591471072 | None | None | N |
| E/R | 0.444 | ambiguous | 0.4264 | ambiguous | 0.291 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| E/S | 0.4022 | ambiguous | 0.3972 | ambiguous | -0.663 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| E/T | 0.3601 | ambiguous | 0.3595 | ambiguous | -0.442 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| E/V | 0.2525 | likely_benign | 0.2429 | benign | -0.102 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | D | 0.576374509 | None | None | N |
| E/W | 0.9571 | likely_pathogenic | 0.9493 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| E/Y | 0.7885 | likely_pathogenic | 0.7695 | pathogenic | 0.055 | Stabilizing | 1.0 | D | 0.641 | 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.