Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33027 | 99304;99305;99306 | chr2:178538750;178538749;178538748 | chr2:179403477;179403476;179403475 |
| N2AB | 31386 | 94381;94382;94383 | chr2:178538750;178538749;178538748 | chr2:179403477;179403476;179403475 |
| N2A | 30459 | 91600;91601;91602 | chr2:178538750;178538749;178538748 | chr2:179403477;179403476;179403475 |
| N2B | 23962 | 72109;72110;72111 | chr2:178538750;178538749;178538748 | chr2:179403477;179403476;179403475 |
| Novex-1 | 24087 | 72484;72485;72486 | chr2:178538750;178538749;178538748 | chr2:179403477;179403476;179403475 |
| Novex-2 | 24154 | 72685;72686;72687 | chr2:178538750;178538749;178538748 | chr2:179403477;179403476;179403475 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | None | None | 1.0 | N | 0.621 | 0.488 | 0.498513350342 | gnomAD-4.0.0 | 1.5914E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.773E-05 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs1060500594  |
None | 1.0 | N | 0.689 | 0.521 | 0.58060787921 | gnomAD-4.0.0 | 6.36562E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43287E-05 | 9.07167E-05 |
| G/S | rs753657854 |
-0.039 | 1.0 | N | 0.701 | 0.46 | 0.505091552036 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30745E-04 | None | 0 | 0 | 0 |
| G/S | rs753657854 |
-0.039 | 1.0 | N | 0.701 | 0.46 | 0.505091552036 | gnomAD-4.0.0 | 9.54879E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.73181E-05 | 6.04851E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.7357 | likely_pathogenic | 0.7718 | pathogenic | -0.193 | Destabilizing | 1.0 | D | 0.621 | neutral | N | 0.505274614 | None | None | I |
| G/C | 0.8283 | likely_pathogenic | 0.8037 | pathogenic | -0.832 | Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.547283249 | None | None | I |
| G/D | 0.846 | likely_pathogenic | 0.8595 | pathogenic | -0.712 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.519771245 | None | None | I |
| G/E | 0.8651 | likely_pathogenic | 0.8763 | pathogenic | -0.881 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| G/F | 0.9772 | likely_pathogenic | 0.9818 | pathogenic | -1.009 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| G/H | 0.934 | likely_pathogenic | 0.9486 | pathogenic | -0.378 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| G/I | 0.9711 | likely_pathogenic | 0.9745 | pathogenic | -0.422 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| G/K | 0.9273 | likely_pathogenic | 0.9334 | pathogenic | -0.731 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| G/L | 0.9536 | likely_pathogenic | 0.9626 | pathogenic | -0.422 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| G/M | 0.9645 | likely_pathogenic | 0.9719 | pathogenic | -0.514 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| G/N | 0.807 | likely_pathogenic | 0.8334 | pathogenic | -0.346 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| G/P | 0.9955 | likely_pathogenic | 0.9962 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| G/Q | 0.8544 | likely_pathogenic | 0.875 | pathogenic | -0.653 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| G/R | 0.8476 | likely_pathogenic | 0.8626 | pathogenic | -0.263 | Destabilizing | 1.0 | D | 0.79 | deleterious | D | 0.525380332 | None | None | I |
| G/S | 0.4867 | ambiguous | 0.5334 | ambiguous | -0.447 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.509553802 | None | None | I |
| G/T | 0.899 | likely_pathogenic | 0.9074 | pathogenic | -0.557 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| G/V | 0.952 | likely_pathogenic | 0.9549 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.794 | deleterious | D | 0.554031199 | None | None | I |
| G/W | 0.9508 | likely_pathogenic | 0.9596 | pathogenic | -1.138 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| G/Y | 0.9523 | likely_pathogenic | 0.9617 | pathogenic | -0.801 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
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.