Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23862 | 71809;71810;71811 | chr2:178574548;178574547;178574546 | chr2:179439275;179439274;179439273 |
| N2AB | 22221 | 66886;66887;66888 | chr2:178574548;178574547;178574546 | chr2:179439275;179439274;179439273 |
| N2A | 21294 | 64105;64106;64107 | chr2:178574548;178574547;178574546 | chr2:179439275;179439274;179439273 |
| N2B | 14797 | 44614;44615;44616 | chr2:178574548;178574547;178574546 | chr2:179439275;179439274;179439273 |
| Novex-1 | 14922 | 44989;44990;44991 | chr2:178574548;178574547;178574546 | chr2:179439275;179439274;179439273 |
| Novex-2 | 14989 | 45190;45191;45192 | chr2:178574548;178574547;178574546 | chr2:179439275;179439274;179439273 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/D | rs774224899  |
-1.326 | 1.0 | N | 0.751 | 0.492 | 0.417081434665 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| H/D | rs774224899 |
-1.326 | 1.0 | N | 0.751 | 0.492 | 0.417081434665 | gnomAD-4.0.0 | 2.05286E-06 | None | None | None | None | N | None | 0 | 2.23614E-05 | None | 0 | 0 | None | 0 | 0 | 1.79914E-06 | 0 | 0 |
| H/Q | None | None | 1.0 | N | 0.771 | 0.254 | 0.187945064343 | gnomAD-4.0.0 | 1.23171E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61922E-05 | 0 | 0 |
| H/R | rs576552787 |
-1.679 | 1.0 | N | 0.755 | 0.373 | 0.353125101423 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| H/R | rs576552787 |
-1.679 | 1.0 | N | 0.755 | 0.373 | 0.353125101423 | 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 |
| H/R | rs576552787 |
-1.679 | 1.0 | N | 0.755 | 0.373 | 0.353125101423 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| H/R | rs576552787 |
-1.679 | 1.0 | N | 0.755 | 0.373 | 0.353125101423 | gnomAD-4.0.0 | 1.85918E-05 | None | None | None | None | N | None | 1.33262E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.28886E-05 | 0 | 3.20164E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.5455 | ambiguous | 0.5272 | ambiguous | -1.493 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| H/C | 0.2183 | likely_benign | 0.2188 | benign | -0.844 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| H/D | 0.6433 | likely_pathogenic | 0.6198 | pathogenic | -1.301 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.50716573 | None | None | N |
| H/E | 0.5968 | likely_pathogenic | 0.567 | pathogenic | -1.157 | Destabilizing | 0.999 | D | 0.643 | neutral | None | None | None | None | N |
| H/F | 0.2566 | likely_benign | 0.2552 | benign | 0.103 | Stabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| H/G | 0.7489 | likely_pathogenic | 0.7286 | pathogenic | -1.867 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| H/I | 0.2815 | likely_benign | 0.2634 | benign | -0.418 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| H/K | 0.5045 | ambiguous | 0.4969 | ambiguous | -1.324 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| H/L | 0.1761 | likely_benign | 0.1695 | benign | -0.418 | Destabilizing | 1.0 | D | 0.773 | deleterious | N | 0.472418438 | None | None | N |
| H/M | 0.5345 | ambiguous | 0.5137 | ambiguous | -0.657 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| H/N | 0.2372 | likely_benign | 0.2354 | benign | -1.54 | Destabilizing | 0.999 | D | 0.631 | neutral | N | 0.494967224 | None | None | N |
| H/P | 0.9557 | likely_pathogenic | 0.9389 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.786 | deleterious | N | 0.502955712 | None | None | N |
| H/Q | 0.3397 | likely_benign | 0.3276 | benign | -1.177 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.502509272 | None | None | N |
| H/R | 0.2098 | likely_benign | 0.2043 | benign | -1.664 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.491868204 | None | None | N |
| H/S | 0.4336 | ambiguous | 0.4227 | ambiguous | -1.639 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| H/T | 0.3774 | ambiguous | 0.3622 | ambiguous | -1.395 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| H/V | 0.2852 | likely_benign | 0.2676 | benign | -0.762 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| H/W | 0.3665 | ambiguous | 0.3593 | ambiguous | 0.467 | Stabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| H/Y | 0.1094 | likely_benign | 0.1061 | benign | 0.432 | Stabilizing | 0.999 | D | 0.649 | neutral | N | 0.466012541 | 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.