Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2106 | 6541;6542;6543 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
| N2AB | 2106 | 6541;6542;6543 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
| N2A | 2106 | 6541;6542;6543 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
| N2B | 2060 | 6403;6404;6405 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
| Novex-1 | 2060 | 6403;6404;6405 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
| Novex-2 | 2060 | 6403;6404;6405 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
| Novex-3 | 2106 | 6541;6542;6543 | chr2:178775548;178775547;178775546 | chr2:179640275;179640274;179640273 |
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/E | None | None | 0.767 | N | 0.231 | 0.171 | 0.253205268125 | gnomAD-4.0.0 | 4.7888E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29519E-06 | 0 | 0 |
| D/H | rs774275945  |
0.022 | 1.0 | N | 0.636 | 0.58 | 0.440810947182 | gnomAD-2.1.1 | 2.83E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.02334E-04 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs774275945 |
0.022 | 1.0 | N | 0.636 | 0.58 | 0.440810947182 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85951E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs774275945 |
0.022 | 1.0 | N | 0.636 | 0.58 | 0.440810947182 | gnomAD-4.0.0 | 4.33739E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.33797E-04 | None | 0 | 0 | 0 | 0 | 1.60046E-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 | 0.4193 | ambiguous | 0.356 | ambiguous | -0.204 | Destabilizing | 0.996 | D | 0.64 | neutral | N | 0.471654344 | None | None | N |
| D/C | 0.9429 | likely_pathogenic | 0.9139 | pathogenic | -0.029 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| D/E | 0.3462 | ambiguous | 0.3002 | benign | -0.263 | Destabilizing | 0.767 | D | 0.231 | neutral | N | 0.402905461 | None | None | N |
| D/F | 0.8085 | likely_pathogenic | 0.7623 | pathogenic | -0.07 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/G | 0.6846 | likely_pathogenic | 0.615 | pathogenic | -0.401 | Destabilizing | 0.998 | D | 0.636 | neutral | N | 0.508318961 | None | None | N |
| D/H | 0.6907 | likely_pathogenic | 0.6337 | pathogenic | 0.179 | Stabilizing | 1.0 | D | 0.636 | neutral | N | 0.504638653 | None | None | N |
| D/I | 0.6406 | likely_pathogenic | 0.574 | pathogenic | 0.267 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/K | 0.7612 | likely_pathogenic | 0.7078 | pathogenic | 0.35 | Stabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | N |
| D/L | 0.6297 | likely_pathogenic | 0.5723 | pathogenic | 0.267 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/M | 0.8399 | likely_pathogenic | 0.7906 | pathogenic | 0.293 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | N |
| D/N | 0.2796 | likely_benign | 0.2286 | benign | -0.015 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | N | 0.501854428 | None | None | N |
| D/P | 0.8314 | likely_pathogenic | 0.7924 | pathogenic | 0.132 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/Q | 0.6942 | likely_pathogenic | 0.6357 | pathogenic | 0.035 | Stabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| D/R | 0.7653 | likely_pathogenic | 0.7217 | pathogenic | 0.555 | Stabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/S | 0.3383 | likely_benign | 0.2843 | benign | -0.109 | Destabilizing | 0.997 | D | 0.661 | neutral | None | None | None | None | N |
| D/T | 0.5667 | likely_pathogenic | 0.5061 | ambiguous | 0.051 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| D/V | 0.4743 | ambiguous | 0.4015 | ambiguous | 0.132 | Stabilizing | 0.999 | D | 0.7 | prob.neutral | N | 0.484890757 | None | None | N |
| D/W | 0.9723 | likely_pathogenic | 0.9656 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Y | 0.5061 | ambiguous | 0.4529 | ambiguous | 0.172 | Stabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.516110765 | 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.