Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2485 | 7678;7679;7680 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
| N2AB | 2485 | 7678;7679;7680 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
| N2A | 2485 | 7678;7679;7680 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
| N2B | 2439 | 7540;7541;7542 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
| Novex-1 | 2439 | 7540;7541;7542 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
| Novex-2 | 2439 | 7540;7541;7542 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
| Novex-3 | 2485 | 7678;7679;7680 | chr2:178773603;178773602;178773601 | chr2:179638330;179638329;179638328 |
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 | rs771849393  |
-0.477 | 0.934 | D | 0.519 | 0.53 | 0.537777371803 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| I/M | rs771849393 |
-0.477 | 0.934 | D | 0.519 | 0.53 | 0.537777371803 | gnomAD-4.0.0 | 4.77205E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57016E-06 | 0 | 0 |
| I/V | None | None | 0.005 | N | 0.144 | 0.221 | 0.370424759081 | gnomAD-4.0.0 | 2.73641E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59727E-06 | 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 | 0.8471 | likely_pathogenic | 0.8444 | pathogenic | -2.126 | Highly Destabilizing | 0.525 | D | 0.487 | neutral | None | None | None | None | N |
| I/C | 0.8945 | likely_pathogenic | 0.8937 | pathogenic | -1.235 | Destabilizing | 0.998 | D | 0.516 | neutral | None | None | None | None | N |
| I/D | 0.9879 | likely_pathogenic | 0.9879 | pathogenic | -2.331 | Highly Destabilizing | 0.991 | D | 0.598 | neutral | None | None | None | None | N |
| I/E | 0.9453 | likely_pathogenic | 0.9431 | pathogenic | -2.145 | Highly Destabilizing | 0.974 | D | 0.595 | neutral | None | None | None | None | N |
| I/F | 0.3621 | ambiguous | 0.3681 | ambiguous | -1.298 | Destabilizing | 0.934 | D | 0.501 | neutral | D | 0.563508459 | None | None | N |
| I/G | 0.9607 | likely_pathogenic | 0.9594 | pathogenic | -2.601 | Highly Destabilizing | 0.974 | D | 0.585 | neutral | None | None | None | None | N |
| I/H | 0.9226 | likely_pathogenic | 0.9223 | pathogenic | -1.93 | Destabilizing | 0.998 | D | 0.588 | neutral | None | None | None | None | N |
| I/K | 0.8474 | likely_pathogenic | 0.8395 | pathogenic | -1.634 | Destabilizing | 0.974 | D | 0.583 | neutral | None | None | None | None | N |
| I/L | 0.1317 | likely_benign | 0.1298 | benign | -0.782 | Destabilizing | 0.002 | N | 0.134 | neutral | N | 0.417714656 | None | None | N |
| I/M | 0.1597 | likely_benign | 0.1615 | benign | -0.611 | Destabilizing | 0.934 | D | 0.519 | neutral | D | 0.546775146 | None | None | N |
| I/N | 0.8689 | likely_pathogenic | 0.8657 | pathogenic | -1.868 | Destabilizing | 0.989 | D | 0.608 | neutral | D | 0.630399613 | None | None | N |
| I/P | 0.9779 | likely_pathogenic | 0.98 | pathogenic | -1.209 | Destabilizing | 0.991 | D | 0.597 | neutral | None | None | None | None | N |
| I/Q | 0.8703 | likely_pathogenic | 0.866 | pathogenic | -1.805 | Destabilizing | 0.991 | D | 0.593 | neutral | None | None | None | None | N |
| I/R | 0.8052 | likely_pathogenic | 0.7935 | pathogenic | -1.295 | Destabilizing | 0.991 | D | 0.609 | neutral | None | None | None | None | N |
| I/S | 0.8952 | likely_pathogenic | 0.8901 | pathogenic | -2.488 | Highly Destabilizing | 0.966 | D | 0.545 | neutral | D | 0.58926283 | None | None | N |
| I/T | 0.8177 | likely_pathogenic | 0.8108 | pathogenic | -2.164 | Highly Destabilizing | 0.801 | D | 0.509 | neutral | D | 0.624116402 | None | None | N |
| I/V | 0.1229 | likely_benign | 0.1228 | benign | -1.209 | Destabilizing | 0.005 | N | 0.144 | neutral | N | 0.433002516 | None | None | N |
| I/W | 0.923 | likely_pathogenic | 0.9273 | pathogenic | -1.625 | Destabilizing | 0.998 | D | 0.625 | neutral | None | None | None | None | N |
| I/Y | 0.8118 | likely_pathogenic | 0.8061 | pathogenic | -1.298 | Destabilizing | 0.991 | D | 0.536 | 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.