Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32674 | 98245;98246;98247 | chr2:178540146;178540145;178540144 | chr2:179404873;179404872;179404871 |
| N2AB | 31033 | 93322;93323;93324 | chr2:178540146;178540145;178540144 | chr2:179404873;179404872;179404871 |
| N2A | 30106 | 90541;90542;90543 | chr2:178540146;178540145;178540144 | chr2:179404873;179404872;179404871 |
| N2B | 23609 | 71050;71051;71052 | chr2:178540146;178540145;178540144 | chr2:179404873;179404872;179404871 |
| Novex-1 | 23734 | 71425;71426;71427 | chr2:178540146;178540145;178540144 | chr2:179404873;179404872;179404871 |
| Novex-2 | 23801 | 71626;71627;71628 | chr2:178540146;178540145;178540144 | chr2:179404873;179404872;179404871 |
| 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/C | rs374471511  |
-1.48 | 1.0 | D | 0.71 | 0.488 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 3.56E-05 | 1.65837E-04 |
| R/C | rs374471511 |
-1.48 | 1.0 | D | 0.71 | 0.488 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs374471511 |
-1.48 | 1.0 | D | 0.71 | 0.488 | None | gnomAD-4.0.0 | 2.10734E-05 | None | None | None | None | N | None | 1.33536E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03466E-05 | 8.78619E-05 | 1.60102E-05 |
| R/H | rs750969198 |
-1.999 | 0.783 | D | 0.438 | 0.402 | 0.330331372229 | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 1.23967E-04 | 0 | None | 0 | 1.53767E-04 | None | 3.27E-05 | None | 0 | 4.69E-05 | 0 |
| R/H | rs750969198 |
-1.999 | 0.783 | D | 0.438 | 0.402 | 0.330331372229 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.06868E-04 | 0 |
| R/H | rs750969198 |
-1.999 | 0.783 | D | 0.438 | 0.402 | 0.330331372229 | gnomAD-4.0.0 | 3.03713E-05 | None | None | None | None | N | None | 6.67646E-05 | 0 | None | 0 | 8.91345E-05 | None | 0 | 0 | 2.79778E-05 | 4.39252E-05 | 4.80323E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9544 | likely_pathogenic | 0.9708 | pathogenic | -1.69 | Destabilizing | 0.996 | D | 0.521 | neutral | None | None | None | None | N |
| R/C | 0.4614 | ambiguous | 0.5372 | ambiguous | -1.645 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | D | 0.533829213 | None | None | N |
| R/D | 0.9922 | likely_pathogenic | 0.9952 | pathogenic | -0.95 | Destabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| R/E | 0.9318 | likely_pathogenic | 0.9572 | pathogenic | -0.729 | Destabilizing | 0.992 | D | 0.531 | neutral | None | None | None | None | N |
| R/F | 0.9591 | likely_pathogenic | 0.9745 | pathogenic | -0.783 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/G | 0.9481 | likely_pathogenic | 0.9695 | pathogenic | -2.041 | Highly Destabilizing | 0.998 | D | 0.535 | neutral | D | 0.556452919 | None | None | N |
| R/H | 0.205 | likely_benign | 0.2046 | benign | -1.878 | Destabilizing | 0.783 | D | 0.438 | neutral | D | 0.527245848 | None | None | N |
| R/I | 0.9195 | likely_pathogenic | 0.9443 | pathogenic | -0.675 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| R/K | 0.4117 | ambiguous | 0.4541 | ambiguous | -1.145 | Destabilizing | 0.99 | D | 0.595 | neutral | None | None | None | None | N |
| R/L | 0.8502 | likely_pathogenic | 0.8919 | pathogenic | -0.675 | Destabilizing | 0.999 | D | 0.543 | neutral | N | 0.517206215 | None | None | N |
| R/M | 0.9286 | likely_pathogenic | 0.9526 | pathogenic | -1.236 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| R/N | 0.958 | likely_pathogenic | 0.9731 | pathogenic | -1.248 | Destabilizing | 0.992 | D | 0.507 | neutral | None | None | None | None | N |
| R/P | 0.9982 | likely_pathogenic | 0.999 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.653 | neutral | D | 0.556959898 | None | None | N |
| R/Q | 0.3559 | ambiguous | 0.429 | ambiguous | -1.014 | Destabilizing | 0.999 | D | 0.521 | neutral | None | None | None | None | N |
| R/S | 0.9574 | likely_pathogenic | 0.9745 | pathogenic | -2.017 | Highly Destabilizing | 0.998 | D | 0.503 | neutral | N | 0.516949045 | None | None | N |
| R/T | 0.9384 | likely_pathogenic | 0.9636 | pathogenic | -1.589 | Destabilizing | 1.0 | D | 0.509 | neutral | None | None | None | None | N |
| R/V | 0.9252 | likely_pathogenic | 0.9507 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/W | 0.6755 | likely_pathogenic | 0.7585 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8662 | likely_pathogenic | 0.9099 | pathogenic | -0.241 | Destabilizing | 0.998 | D | 0.645 | 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.