Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2857 | 8794;8795;8796 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
| N2AB | 2857 | 8794;8795;8796 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
| N2A | 2857 | 8794;8795;8796 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
| N2B | 2811 | 8656;8657;8658 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
| Novex-1 | 2811 | 8656;8657;8658 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
| Novex-2 | 2811 | 8656;8657;8658 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
| Novex-3 | 2857 | 8794;8795;8796 | chr2:178770132;178770131;178770130 | chr2:179634859;179634858;179634857 |
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 | rs1003498795  |
None | 0.602 | D | 0.446 | 0.256 | 0.422160833541 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/C | rs1003498795 |
None | 0.602 | D | 0.446 | 0.256 | 0.422160833541 | gnomAD-4.0.0 | 1.23913E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69489E-06 | 0 | 0 |
| S/F | rs1003498795 |
None | 0.602 | N | 0.473 | 0.246 | 0.554315986709 | gnomAD-4.0.0 | 1.36813E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-06 | 0 | 0 |
| S/Y | None | None | 0.602 | D | 0.473 | 0.306 | 0.59904029974 | gnomAD-4.0.0 | 4.78845E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39576E-06 | 1.15931E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0654 | likely_benign | 0.0586 | benign | -0.635 | Destabilizing | None | N | 0.097 | neutral | N | 0.475629951 | None | None | N |
| S/C | 0.0962 | likely_benign | 0.1042 | benign | -0.423 | Destabilizing | 0.602 | D | 0.446 | neutral | D | 0.53897168 | None | None | N |
| S/D | 0.3089 | likely_benign | 0.3285 | benign | -0.308 | Destabilizing | None | N | 0.166 | neutral | None | None | None | None | N |
| S/E | 0.3618 | ambiguous | 0.3334 | benign | -0.35 | Destabilizing | 0.002 | N | 0.115 | neutral | None | None | None | None | N |
| S/F | 0.1536 | likely_benign | 0.1625 | benign | -1.033 | Destabilizing | 0.602 | D | 0.473 | neutral | N | 0.512059767 | None | None | N |
| S/G | 0.0979 | likely_benign | 0.1087 | benign | -0.832 | Destabilizing | 0.025 | N | 0.317 | neutral | None | None | None | None | N |
| S/H | 0.2768 | likely_benign | 0.2922 | benign | -1.407 | Destabilizing | 0.667 | D | 0.453 | neutral | None | None | None | None | N |
| S/I | 0.1341 | likely_benign | 0.1452 | benign | -0.23 | Destabilizing | 0.124 | N | 0.461 | neutral | None | None | None | None | N |
| S/K | 0.4638 | ambiguous | 0.4457 | ambiguous | -0.67 | Destabilizing | 0.104 | N | 0.315 | neutral | None | None | None | None | N |
| S/L | 0.0731 | likely_benign | 0.0779 | benign | -0.23 | Destabilizing | 0.055 | N | 0.378 | neutral | None | None | None | None | N |
| S/M | 0.1293 | likely_benign | 0.1354 | benign | 0.187 | Stabilizing | 0.667 | D | 0.453 | neutral | None | None | None | None | N |
| S/N | 0.1343 | likely_benign | 0.1607 | benign | -0.563 | Destabilizing | 0.002 | N | 0.11 | neutral | None | None | None | None | N |
| S/P | 0.6643 | likely_pathogenic | 0.6871 | pathogenic | -0.333 | Destabilizing | 0.301 | N | 0.443 | neutral | D | 0.538132235 | None | None | N |
| S/Q | 0.3319 | likely_benign | 0.3201 | benign | -0.807 | Destabilizing | 0.22 | N | 0.342 | neutral | None | None | None | None | N |
| S/R | 0.4179 | ambiguous | 0.4268 | ambiguous | -0.495 | Destabilizing | 0.22 | N | 0.45 | neutral | None | None | None | None | N |
| S/T | 0.0668 | likely_benign | 0.0708 | benign | -0.605 | Destabilizing | None | N | 0.108 | neutral | N | 0.451005276 | None | None | N |
| S/V | 0.1215 | likely_benign | 0.1242 | benign | -0.333 | Destabilizing | 0.055 | N | 0.377 | neutral | None | None | None | None | N |
| S/W | 0.3349 | likely_benign | 0.3526 | ambiguous | -1.002 | Destabilizing | 0.958 | D | 0.484 | neutral | None | None | None | None | N |
| S/Y | 0.1673 | likely_benign | 0.17 | benign | -0.733 | Destabilizing | 0.602 | D | 0.473 | neutral | D | 0.581068828 | 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.