Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16453 | 49582;49583;49584 | chr2:178613926;178613925;178613924 | chr2:179478653;179478652;179478651 |
| N2AB | 14812 | 44659;44660;44661 | chr2:178613926;178613925;178613924 | chr2:179478653;179478652;179478651 |
| N2A | 13885 | 41878;41879;41880 | chr2:178613926;178613925;178613924 | chr2:179478653;179478652;179478651 |
| N2B | 7388 | 22387;22388;22389 | chr2:178613926;178613925;178613924 | chr2:179478653;179478652;179478651 |
| Novex-1 | 7513 | 22762;22763;22764 | chr2:178613926;178613925;178613924 | chr2:179478653;179478652;179478651 |
| Novex-2 | 7580 | 22963;22964;22965 | chr2:178613926;178613925;178613924 | chr2:179478653;179478652;179478651 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs376498195  |
-0.74 | 0.989 | D | 0.803 | 0.464 | None | gnomAD-2.1.1 | 1.45E-05 | None | None | None | None | N | None | 1.66196E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs376498195 |
-0.74 | 0.989 | D | 0.803 | 0.464 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs376498195 |
-0.74 | 0.989 | D | 0.803 | 0.464 | None | gnomAD-4.0.0 | 5.16582E-06 | None | None | None | None | N | None | 6.81013E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs200121902 |
-1.287 | 0.989 | D | 0.723 | 0.424 | None | gnomAD-2.1.1 | 1.85035E-04 | None | None | None | None | N | None | 2.03539E-03 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.9E-06 | 0 |
| P/T | rs200121902 |
-1.287 | 0.989 | D | 0.723 | 0.424 | None | gnomAD-3.1.2 | 5.39744E-04 | None | None | None | None | N | None | 1.93171E-03 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78469E-04 |
| P/T | rs200121902 |
-1.287 | 0.989 | D | 0.723 | 0.424 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 1.5E-03 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| P/T | rs200121902 |
-1.287 | 0.989 | D | 0.723 | 0.424 | None | gnomAD-4.0.0 | 9.64065E-05 | None | None | None | None | N | None | 1.96882E-03 | 1.68936E-05 | None | 0 | 0 | None | 0 | 0 | 8.49749E-07 | 0 | 9.64816E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0919 | likely_benign | 0.0871 | benign | -1.407 | Destabilizing | 0.333 | N | 0.377 | neutral | N | 0.46691514 | None | None | N |
| P/C | 0.5616 | ambiguous | 0.5457 | ambiguous | -1.095 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| P/D | 0.9069 | likely_pathogenic | 0.8862 | pathogenic | -1.857 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| P/E | 0.5575 | ambiguous | 0.5147 | ambiguous | -1.905 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/F | 0.7247 | likely_pathogenic | 0.698 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| P/G | 0.6266 | likely_pathogenic | 0.5842 | pathogenic | -1.661 | Destabilizing | 0.992 | D | 0.743 | deleterious | None | None | None | None | N |
| P/H | 0.511 | ambiguous | 0.4917 | ambiguous | -1.203 | Destabilizing | 1.0 | D | 0.789 | deleterious | D | 0.651085235 | None | None | N |
| P/I | 0.5507 | ambiguous | 0.5305 | ambiguous | -0.821 | Destabilizing | 0.999 | D | 0.821 | deleterious | None | None | None | None | N |
| P/K | 0.6982 | likely_pathogenic | 0.6548 | pathogenic | -1.09 | Destabilizing | 0.999 | D | 0.742 | deleterious | None | None | None | None | N |
| P/L | 0.3645 | ambiguous | 0.35 | ambiguous | -0.821 | Destabilizing | 0.989 | D | 0.803 | deleterious | D | 0.63818547 | None | None | N |
| P/M | 0.4834 | ambiguous | 0.4657 | ambiguous | -0.584 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| P/N | 0.7476 | likely_pathogenic | 0.7236 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/Q | 0.3255 | likely_benign | 0.3032 | benign | -1.222 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | N |
| P/R | 0.5387 | ambiguous | 0.5105 | ambiguous | -0.512 | Destabilizing | 0.998 | D | 0.791 | deleterious | D | 0.609771018 | None | None | N |
| P/S | 0.2419 | likely_benign | 0.2272 | benign | -1.318 | Destabilizing | 0.978 | D | 0.689 | prob.neutral | N | 0.476147314 | None | None | N |
| P/T | 0.2999 | likely_benign | 0.287 | benign | -1.272 | Destabilizing | 0.989 | D | 0.723 | prob.delet. | D | 0.649559585 | None | None | N |
| P/V | 0.4194 | ambiguous | 0.3892 | ambiguous | -0.984 | Destabilizing | 0.992 | D | 0.765 | deleterious | None | None | None | None | N |
| P/W | 0.9041 | likely_pathogenic | 0.8958 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| P/Y | 0.7544 | likely_pathogenic | 0.7418 | pathogenic | -1.222 | Destabilizing | 1.0 | D | 0.837 | 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.