Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30265 | 91018;91019;91020 | chr2:178552107;178552106;178552105 | chr2:179416834;179416833;179416832 |
| N2AB | 28624 | 86095;86096;86097 | chr2:178552107;178552106;178552105 | chr2:179416834;179416833;179416832 |
| N2A | 27697 | 83314;83315;83316 | chr2:178552107;178552106;178552105 | chr2:179416834;179416833;179416832 |
| N2B | 21200 | 63823;63824;63825 | chr2:178552107;178552106;178552105 | chr2:179416834;179416833;179416832 |
| Novex-1 | 21325 | 64198;64199;64200 | chr2:178552107;178552106;178552105 | chr2:179416834;179416833;179416832 |
| Novex-2 | 21392 | 64399;64400;64401 | chr2:178552107;178552106;178552105 | chr2:179416834;179416833;179416832 |
| 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/G | None | None | 1.0 | N | 0.749 | 0.551 | 0.484329738948 | gnomAD-4.0.0 | 1.3685E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31976E-05 | 0 |
| R/Q | rs771164863  |
-1.009 | 1.0 | N | 0.685 | 0.505 | 0.312608672186 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| R/Q | rs771164863 |
-1.009 | 1.0 | N | 0.685 | 0.505 | 0.312608672186 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs771164863 |
-1.009 | 1.0 | N | 0.685 | 0.505 | 0.312608672186 | gnomAD-4.0.0 | 9.91627E-06 | None | None | None | None | N | None | 1.33554E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10196E-05 | 2.19717E-05 | 0 |
| R/W | rs200022152 |
-1.348 | 1.0 | N | 0.883 | 0.48 | None | gnomAD-2.1.1 | 9.29E-05 | None | None | None | None | N | None | 2.06629E-04 | 2.83E-05 | None | 0 | 0 | None | 9.82E-05 | None | 1.20221E-04 | 1.01551E-04 | 1.40489E-04 |
| R/W | rs200022152 |
-1.348 | 1.0 | N | 0.883 | 0.48 | None | gnomAD-3.1.2 | 1.44665E-04 | None | None | None | None | N | None | 2.89673E-04 | 0 | 0 | 0 | 0 | None | 2.82912E-04 | 0 | 7.35E-05 | 2.06868E-04 | 4.79386E-04 |
| R/W | rs200022152 |
-1.348 | 1.0 | N | 0.883 | 0.48 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/W | rs200022152 |
-1.348 | 1.0 | N | 0.883 | 0.48 | None | gnomAD-4.0.0 | 8.11825E-05 | None | None | None | None | N | None | 2.93279E-04 | 1.66728E-05 | None | 0 | 0 | None | 9.37734E-05 | 1.65071E-04 | 7.54412E-05 | 8.78677E-05 | 6.40225E-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 | 0.9409 | likely_pathogenic | 0.904 | pathogenic | -1.973 | Destabilizing | 0.999 | D | 0.507 | neutral | None | None | None | None | N |
| R/C | 0.4079 | ambiguous | 0.3251 | benign | -1.932 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| R/D | 0.9945 | likely_pathogenic | 0.9918 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| R/E | 0.924 | likely_pathogenic | 0.8924 | pathogenic | -0.674 | Destabilizing | 0.999 | D | 0.554 | neutral | None | None | None | None | N |
| R/F | 0.9561 | likely_pathogenic | 0.9388 | pathogenic | -1.262 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| R/G | 0.9143 | likely_pathogenic | 0.8743 | pathogenic | -2.329 | Highly Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.511606674 | None | None | N |
| R/H | 0.4747 | ambiguous | 0.4056 | ambiguous | -2.15 | Highly Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| R/I | 0.8926 | likely_pathogenic | 0.8423 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/K | 0.2505 | likely_benign | 0.2252 | benign | -1.489 | Destabilizing | 0.998 | D | 0.483 | neutral | None | None | None | None | N |
| R/L | 0.8102 | likely_pathogenic | 0.7475 | pathogenic | -0.946 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.4994899 | None | None | N |
| R/M | 0.7577 | likely_pathogenic | 0.6668 | pathogenic | -1.367 | Destabilizing | 1.0 | D | 0.846 | deleterious | None | None | None | None | N |
| R/N | 0.9762 | likely_pathogenic | 0.9618 | pathogenic | -1.342 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| R/P | 0.9988 | likely_pathogenic | 0.9983 | pathogenic | -1.275 | Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.532597764 | None | None | N |
| R/Q | 0.2942 | likely_benign | 0.2302 | benign | -1.281 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.485852189 | None | None | N |
| R/S | 0.9737 | likely_pathogenic | 0.9539 | pathogenic | -2.295 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/T | 0.932 | likely_pathogenic | 0.8782 | pathogenic | -1.87 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/V | 0.9087 | likely_pathogenic | 0.863 | pathogenic | -1.275 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| R/W | 0.7372 | likely_pathogenic | 0.6883 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.883 | deleterious | N | 0.504832271 | None | None | N |
| R/Y | 0.878 | likely_pathogenic | 0.841 | pathogenic | -0.58 | Destabilizing | 1.0 | D | 0.905 | 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.