Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26911 | 80956;80957;80958 | chr2:178565401;178565400;178565399 | chr2:179430128;179430127;179430126 |
| N2AB | 25270 | 76033;76034;76035 | chr2:178565401;178565400;178565399 | chr2:179430128;179430127;179430126 |
| N2A | 24343 | 73252;73253;73254 | chr2:178565401;178565400;178565399 | chr2:179430128;179430127;179430126 |
| N2B | 17846 | 53761;53762;53763 | chr2:178565401;178565400;178565399 | chr2:179430128;179430127;179430126 |
| Novex-1 | 17971 | 54136;54137;54138 | chr2:178565401;178565400;178565399 | chr2:179430128;179430127;179430126 |
| Novex-2 | 18038 | 54337;54338;54339 | chr2:178565401;178565400;178565399 | chr2:179430128;179430127;179430126 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs371965190  |
-0.661 | 0.782 | D | 0.699 | 0.463 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 1.65412E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs371965190 |
-0.661 | 0.782 | D | 0.699 | 0.463 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 1.44802E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs371965190 |
-0.661 | 0.782 | D | 0.699 | 0.463 | None | gnomAD-4.0.0 | 9.29593E-06 | None | None | None | None | N | None | 1.86632E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09803E-05 | 0 |
| I/V | rs1017295644 |
None | None | N | 0.282 | 0.18 | 0.159798565429 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.75482E-04 | None | 0 | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5298 | ambiguous | 0.4805 | ambiguous | -2.116 | Highly Destabilizing | 0.218 | N | 0.709 | prob.delet. | None | None | None | None | N |
| I/C | 0.6541 | likely_pathogenic | 0.6041 | pathogenic | -1.441 | Destabilizing | 0.973 | D | 0.775 | deleterious | None | None | None | None | N |
| I/D | 0.9451 | likely_pathogenic | 0.9379 | pathogenic | -1.491 | Destabilizing | 0.906 | D | 0.85 | deleterious | None | None | None | None | N |
| I/E | 0.9208 | likely_pathogenic | 0.9154 | pathogenic | -1.429 | Destabilizing | 0.906 | D | 0.833 | deleterious | None | None | None | None | N |
| I/F | 0.213 | likely_benign | 0.1933 | benign | -1.453 | Destabilizing | 0.782 | D | 0.702 | prob.neutral | N | 0.512024062 | None | None | N |
| I/G | 0.8298 | likely_pathogenic | 0.7949 | pathogenic | -2.52 | Highly Destabilizing | 0.906 | D | 0.824 | deleterious | None | None | None | None | N |
| I/H | 0.8121 | likely_pathogenic | 0.7971 | pathogenic | -1.694 | Destabilizing | 0.991 | D | 0.857 | deleterious | None | None | None | None | N |
| I/K | 0.7612 | likely_pathogenic | 0.7697 | pathogenic | -1.473 | Destabilizing | 0.906 | D | 0.834 | deleterious | None | None | None | None | N |
| I/L | 0.1486 | likely_benign | 0.136 | benign | -1.037 | Destabilizing | 0.084 | N | 0.411 | neutral | N | 0.49799473 | None | None | N |
| I/M | 0.1775 | likely_benign | 0.1623 | benign | -0.856 | Destabilizing | 0.782 | D | 0.699 | prob.neutral | D | 0.550892371 | None | None | N |
| I/N | 0.6473 | likely_pathogenic | 0.6393 | pathogenic | -1.358 | Destabilizing | 0.957 | D | 0.861 | deleterious | D | 0.544815985 | None | None | N |
| I/P | 0.8879 | likely_pathogenic | 0.8749 | pathogenic | -1.368 | Destabilizing | 0.967 | D | 0.86 | deleterious | None | None | None | None | N |
| I/Q | 0.8218 | likely_pathogenic | 0.8072 | pathogenic | -1.464 | Destabilizing | 0.967 | D | 0.855 | deleterious | None | None | None | None | N |
| I/R | 0.6803 | likely_pathogenic | 0.6854 | pathogenic | -0.922 | Destabilizing | 0.906 | D | 0.861 | deleterious | None | None | None | None | N |
| I/S | 0.5879 | likely_pathogenic | 0.5501 | ambiguous | -2.078 | Highly Destabilizing | 0.782 | D | 0.829 | deleterious | D | 0.536168704 | None | None | N |
| I/T | 0.4135 | ambiguous | 0.3779 | ambiguous | -1.878 | Destabilizing | 0.505 | D | 0.716 | prob.delet. | N | 0.506454654 | None | None | N |
| I/V | 0.0694 | likely_benign | 0.0631 | benign | -1.368 | Destabilizing | None | N | 0.282 | neutral | N | 0.443410614 | None | None | N |
| I/W | 0.8906 | likely_pathogenic | 0.8783 | pathogenic | -1.538 | Destabilizing | 0.991 | D | 0.846 | deleterious | None | None | None | None | N |
| I/Y | 0.6555 | likely_pathogenic | 0.6309 | pathogenic | -1.33 | Destabilizing | 0.906 | D | 0.777 | deleterious | 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.