Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3367 | 10324;10325;10326 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
| N2AB | 3367 | 10324;10325;10326 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
| N2A | 3367 | 10324;10325;10326 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
| N2B | 3321 | 10186;10187;10188 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
| Novex-1 | 3321 | 10186;10187;10188 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
| Novex-2 | 3321 | 10186;10187;10188 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
| Novex-3 | 3367 | 10324;10325;10326 | chr2:178764192;178764191;178764190 | chr2:179628919;179628918;179628917 |
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/Q | rs34819099  |
-1.188 | 0.005 | N | 0.303 | 0.051 | None | gnomAD-2.1.1 | 1.00805E-02 | None | None | None | None | N | None | 2.68387E-03 | 5.05222E-03 | None | 2.23809E-02 | 9.53145E-04 | None | 6.72851E-03 | None | 2.18932E-03 | 1.55964E-02 | 1.09358E-02 |
| R/Q | rs34819099 |
-1.188 | 0.005 | N | 0.303 | 0.051 | None | gnomAD-3.1.2 | 9.615E-03 | None | None | None | None | N | None | 3.0167E-03 | 6.02568E-03 | 1.75439E-02 | 1.92972E-02 | 5.7759E-04 | None | 3.01659E-03 | 9.49367E-03 | 1.57123E-02 | 7.66363E-03 | 9.09962E-03 |
| R/Q | rs34819099 |
-1.188 | 0.005 | N | 0.303 | 0.051 | None | 1000 genomes | 3.79393E-03 | None | None | None | None | N | None | 0 | 2.9E-03 | None | None | 1E-03 | 1.29E-02 | None | None | None | 3.1E-03 | None |
| R/Q | rs34819099 |
-1.188 | 0.005 | N | 0.303 | 0.051 | None | gnomAD-4.0.0 | 1.47477E-02 | None | None | None | None | N | None | 2.82531E-03 | 5.6822E-03 | None | 2.19888E-02 | 1.20332E-03 | None | 2.70211E-03 | 5.27879E-03 | 1.75878E-02 | 7.19148E-03 | 1.46711E-02 |
| R/W | rs762791706 |
-0.793 | 0.984 | D | 0.607 | 0.391 | 0.42081714158 | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.44E-05 | None | 0 | None | 0 | 8.8E-06 | 0 |
| R/W | rs762791706 |
-0.793 | 0.984 | D | 0.607 | 0.391 | 0.42081714158 | gnomAD-4.0.0 | 2.46272E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.51179E-04 | None | 0 | 1.7337E-04 | 2.33826E-05 | 1.15934E-05 | 3.3117E-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 | 0.4894 | ambiguous | 0.303 | benign | -1.209 | Destabilizing | 0.035 | N | 0.485 | neutral | None | None | None | None | N |
| R/C | 0.2985 | likely_benign | 0.1581 | benign | -1.297 | Destabilizing | 0.824 | D | 0.59 | neutral | None | None | None | None | N |
| R/D | 0.8464 | likely_pathogenic | 0.7056 | pathogenic | -0.577 | Destabilizing | 0.149 | N | 0.574 | neutral | None | None | None | None | N |
| R/E | 0.4494 | ambiguous | 0.3292 | benign | -0.465 | Destabilizing | 0.081 | N | 0.441 | neutral | None | None | None | None | N |
| R/F | 0.6929 | likely_pathogenic | 0.4988 | ambiguous | -1.13 | Destabilizing | 0.555 | D | 0.594 | neutral | None | None | None | None | N |
| R/G | 0.461 | ambiguous | 0.2256 | benign | -1.502 | Destabilizing | 0.251 | N | 0.531 | neutral | D | 0.6101846 | None | None | N |
| R/H | 0.13 | likely_benign | 0.1018 | benign | -1.587 | Destabilizing | 0.38 | N | 0.519 | neutral | None | None | None | None | N |
| R/I | 0.3399 | likely_benign | 0.2276 | benign | -0.414 | Destabilizing | 0.235 | N | 0.603 | neutral | None | None | None | None | N |
| R/K | 0.145 | likely_benign | 0.1148 | benign | -1.449 | Destabilizing | 0.001 | N | 0.189 | neutral | None | None | None | None | N |
| R/L | 0.3302 | likely_benign | 0.2102 | benign | -0.414 | Destabilizing | 0.144 | N | 0.543 | neutral | D | 0.537222711 | None | None | N |
| R/M | 0.3945 | ambiguous | 0.2481 | benign | -0.603 | Destabilizing | 0.555 | D | 0.573 | neutral | None | None | None | None | N |
| R/N | 0.7368 | likely_pathogenic | 0.5289 | ambiguous | -0.867 | Destabilizing | 0.149 | N | 0.453 | neutral | None | None | None | None | N |
| R/P | 0.9446 | likely_pathogenic | 0.8646 | pathogenic | -0.661 | Destabilizing | 0.705 | D | 0.595 | neutral | D | 0.593364842 | None | None | N |
| R/Q | 0.1029 | likely_benign | 0.0877 | benign | -1.093 | Destabilizing | 0.005 | N | 0.303 | neutral | N | 0.499174197 | None | None | N |
| R/S | 0.5479 | ambiguous | 0.3379 | benign | -1.672 | Destabilizing | 0.081 | N | 0.485 | neutral | None | None | None | None | N |
| R/T | 0.2818 | likely_benign | 0.1601 | benign | -1.391 | Destabilizing | None | N | 0.23 | neutral | None | None | None | None | N |
| R/V | 0.4042 | ambiguous | 0.278 | benign | -0.661 | Destabilizing | 0.081 | N | 0.579 | neutral | None | None | None | None | N |
| R/W | 0.3175 | likely_benign | 0.209 | benign | -0.727 | Destabilizing | 0.984 | D | 0.607 | neutral | D | 0.651508214 | None | None | N |
| R/Y | 0.5636 | ambiguous | 0.3911 | ambiguous | -0.439 | Destabilizing | 0.555 | D | 0.593 | 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.