Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25157 | 75694;75695;75696 | chr2:178570663;178570662;178570661 | chr2:179435390;179435389;179435388 |
| N2AB | 23516 | 70771;70772;70773 | chr2:178570663;178570662;178570661 | chr2:179435390;179435389;179435388 |
| N2A | 22589 | 67990;67991;67992 | chr2:178570663;178570662;178570661 | chr2:179435390;179435389;179435388 |
| N2B | 16092 | 48499;48500;48501 | chr2:178570663;178570662;178570661 | chr2:179435390;179435389;179435388 |
| Novex-1 | 16217 | 48874;48875;48876 | chr2:178570663;178570662;178570661 | chr2:179435390;179435389;179435388 |
| Novex-2 | 16284 | 49075;49076;49077 | chr2:178570663;178570662;178570661 | chr2:179435390;179435389;179435388 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.722 | N | 0.433 | 0.305 | 0.405700215632 | gnomAD-4.0.0 | 6.84339E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99588E-07 | 0 | 0 |
| R/Q | rs779410073  |
-0.079 | 0.742 | N | 0.454 | 0.249 | 0.107399877778 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.33E-05 | 0 |
| R/Q | rs779410073 |
-0.079 | 0.742 | N | 0.454 | 0.249 | 0.107399877778 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs779410073 |
-0.079 | 0.742 | N | 0.454 | 0.249 | 0.107399877778 | gnomAD-4.0.0 | 8.67763E-06 | None | None | None | None | N | None | 1.33536E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10206E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6179 | likely_pathogenic | 0.6728 | pathogenic | -0.557 | Destabilizing | 0.575 | D | 0.417 | neutral | None | None | None | None | N |
| R/C | 0.2334 | likely_benign | 0.2631 | benign | -0.411 | Destabilizing | 0.991 | D | 0.605 | neutral | None | None | None | None | N |
| R/D | 0.8065 | likely_pathogenic | 0.8371 | pathogenic | 0.07 | Stabilizing | 0.404 | N | 0.444 | neutral | None | None | None | None | N |
| R/E | 0.6383 | likely_pathogenic | 0.6649 | pathogenic | 0.189 | Stabilizing | 0.004 | N | 0.236 | neutral | None | None | None | None | N |
| R/F | 0.6405 | likely_pathogenic | 0.7166 | pathogenic | -0.411 | Destabilizing | 0.826 | D | 0.536 | neutral | None | None | None | None | N |
| R/G | 0.4264 | ambiguous | 0.4879 | ambiguous | -0.871 | Destabilizing | 0.722 | D | 0.44 | neutral | N | 0.491085066 | None | None | N |
| R/H | 0.1422 | likely_benign | 0.1385 | benign | -1.255 | Destabilizing | 0.01 | N | 0.293 | neutral | None | None | None | None | N |
| R/I | 0.4591 | ambiguous | 0.5164 | ambiguous | 0.28 | Stabilizing | 0.906 | D | 0.525 | neutral | None | None | None | None | N |
| R/K | 0.1589 | likely_benign | 0.1689 | benign | -0.559 | Destabilizing | 0.218 | N | 0.429 | neutral | None | None | None | None | N |
| R/L | 0.3406 | ambiguous | 0.4091 | ambiguous | 0.28 | Stabilizing | 0.722 | D | 0.433 | neutral | N | 0.495212896 | None | None | N |
| R/M | 0.4541 | ambiguous | 0.5194 | ambiguous | -0.05 | Destabilizing | 0.991 | D | 0.415 | neutral | None | None | None | None | N |
| R/N | 0.6711 | likely_pathogenic | 0.7094 | pathogenic | -0.01 | Destabilizing | 0.404 | N | 0.409 | neutral | None | None | None | None | N |
| R/P | 0.8537 | likely_pathogenic | 0.8826 | pathogenic | 0.022 | Stabilizing | 0.949 | D | 0.481 | neutral | D | 0.53004228 | None | None | N |
| R/Q | 0.161 | likely_benign | 0.1679 | benign | -0.161 | Destabilizing | 0.742 | D | 0.454 | neutral | N | 0.50032823 | None | None | N |
| R/S | 0.6717 | likely_pathogenic | 0.7218 | pathogenic | -0.71 | Destabilizing | 0.575 | D | 0.433 | neutral | None | None | None | None | N |
| R/T | 0.467 | ambiguous | 0.5214 | ambiguous | -0.41 | Destabilizing | 0.575 | D | 0.423 | neutral | None | None | None | None | N |
| R/V | 0.5786 | likely_pathogenic | 0.612 | pathogenic | 0.022 | Stabilizing | 0.906 | D | 0.526 | neutral | None | None | None | None | N |
| R/W | 0.2408 | likely_benign | 0.28 | benign | -0.124 | Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | N |
| R/Y | 0.4333 | ambiguous | 0.5055 | ambiguous | 0.189 | Stabilizing | 0.704 | D | 0.483 | 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.