Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19510 | 58753;58754;58755 | chr2:178593772;178593771;178593770 | chr2:179458499;179458498;179458497 |
| N2AB | 17869 | 53830;53831;53832 | chr2:178593772;178593771;178593770 | chr2:179458499;179458498;179458497 |
| N2A | 16942 | 51049;51050;51051 | chr2:178593772;178593771;178593770 | chr2:179458499;179458498;179458497 |
| N2B | 10445 | 31558;31559;31560 | chr2:178593772;178593771;178593770 | chr2:179458499;179458498;179458497 |
| Novex-1 | 10570 | 31933;31934;31935 | chr2:178593772;178593771;178593770 | chr2:179458499;179458498;179458497 |
| Novex-2 | 10637 | 32134;32135;32136 | chr2:178593772;178593771;178593770 | chr2:179458499;179458498;179458497 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.704 | N | 0.545 | 0.156 | 0.222439326576 | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02608E-05 |
| S/N | rs1209004438  |
None | 0.986 | N | 0.65 | 0.339 | 0.307966526162 | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85943E-06 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1338 | likely_benign | 0.1312 | benign | -0.886 | Destabilizing | 0.079 | N | 0.33 | neutral | None | None | None | None | I |
| S/C | 0.1175 | likely_benign | 0.1168 | benign | -0.575 | Destabilizing | 0.035 | N | 0.413 | neutral | N | 0.508094024 | None | None | I |
| S/D | 0.7809 | likely_pathogenic | 0.8223 | pathogenic | -0.294 | Destabilizing | 0.969 | D | 0.633 | neutral | None | None | None | None | I |
| S/E | 0.8046 | likely_pathogenic | 0.8382 | pathogenic | -0.287 | Destabilizing | 0.969 | D | 0.631 | neutral | None | None | None | None | I |
| S/F | 0.6019 | likely_pathogenic | 0.6082 | pathogenic | -1.073 | Destabilizing | 0.997 | D | 0.657 | neutral | None | None | None | None | I |
| S/G | 0.1886 | likely_benign | 0.1819 | benign | -1.14 | Destabilizing | 0.704 | D | 0.545 | neutral | N | 0.471312197 | None | None | I |
| S/H | 0.7205 | likely_pathogenic | 0.7727 | pathogenic | -1.579 | Destabilizing | 0.999 | D | 0.612 | neutral | None | None | None | None | I |
| S/I | 0.5246 | ambiguous | 0.5287 | ambiguous | -0.312 | Destabilizing | 0.988 | D | 0.671 | neutral | N | 0.502705904 | None | None | I |
| S/K | 0.9502 | likely_pathogenic | 0.9627 | pathogenic | -0.731 | Destabilizing | 0.939 | D | 0.63 | neutral | None | None | None | None | I |
| S/L | 0.2986 | likely_benign | 0.2957 | benign | -0.312 | Destabilizing | 0.939 | D | 0.589 | neutral | None | None | None | None | I |
| S/M | 0.4301 | ambiguous | 0.425 | ambiguous | 0.042 | Stabilizing | 0.997 | D | 0.619 | neutral | None | None | None | None | I |
| S/N | 0.3886 | ambiguous | 0.4305 | ambiguous | -0.72 | Destabilizing | 0.986 | D | 0.65 | neutral | N | 0.491349598 | None | None | I |
| S/P | 0.9786 | likely_pathogenic | 0.977 | pathogenic | -0.47 | Destabilizing | 0.991 | D | 0.641 | neutral | None | None | None | None | I |
| S/Q | 0.7844 | likely_pathogenic | 0.815 | pathogenic | -0.867 | Destabilizing | 0.997 | D | 0.636 | neutral | None | None | None | None | I |
| S/R | 0.9221 | likely_pathogenic | 0.9337 | pathogenic | -0.632 | Destabilizing | 0.988 | D | 0.644 | neutral | N | 0.486359168 | None | None | I |
| S/T | 0.232 | likely_benign | 0.2094 | benign | -0.755 | Destabilizing | 0.826 | D | 0.566 | neutral | N | 0.476777289 | None | None | I |
| S/V | 0.4519 | ambiguous | 0.4326 | ambiguous | -0.47 | Destabilizing | 0.939 | D | 0.627 | neutral | None | None | None | None | I |
| S/W | 0.7522 | likely_pathogenic | 0.7474 | pathogenic | -1.02 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | I |
| S/Y | 0.5379 | ambiguous | 0.5834 | pathogenic | -0.768 | Destabilizing | 0.997 | D | 0.655 | neutral | 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.