Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33350 | 100273;100274;100275 | chr2:178537061;178537060;178537059 | chr2:179401788;179401787;179401786 |
| N2AB | 31709 | 95350;95351;95352 | chr2:178537061;178537060;178537059 | chr2:179401788;179401787;179401786 |
| N2A | 30782 | 92569;92570;92571 | chr2:178537061;178537060;178537059 | chr2:179401788;179401787;179401786 |
| N2B | 24285 | 73078;73079;73080 | chr2:178537061;178537060;178537059 | chr2:179401788;179401787;179401786 |
| Novex-1 | 24410 | 73453;73454;73455 | chr2:178537061;178537060;178537059 | chr2:179401788;179401787;179401786 |
| Novex-2 | 24477 | 73654;73655;73656 | chr2:178537061;178537060;178537059 | chr2:179401788;179401787;179401786 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs370300135  |
0.301 | 0.946 | N | 0.754 | 0.379 | None | gnomAD-2.1.1 | 1.25489E-04 | None | None | None | None | N | None | 2.90939E-04 | 0 | None | 0 | 1.3929E-03 | None | 0 | None | 0 | 0 | 1.40885E-04 |
| T/I | rs370300135 |
0.301 | 0.946 | N | 0.754 | 0.379 | None | gnomAD-3.1.2 | 1.64292E-04 | None | None | None | None | N | None | 3.86194E-04 | 0 | 0 | 0 | 1.7341E-03 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs370300135 |
0.301 | 0.946 | N | 0.754 | 0.379 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| T/I | rs370300135 |
0.301 | 0.946 | N | 0.754 | 0.379 | None | gnomAD-4.0.0 | 4.52519E-05 | None | None | None | None | N | None | 2.66667E-04 | 0 | None | 0 | 8.7038E-04 | None | 0 | 0 | 2.54334E-06 | 1.09926E-05 | 1.60133E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1266 | likely_benign | 0.1284 | benign | -0.824 | Destabilizing | 0.51 | D | 0.519 | neutral | N | 0.511824975 | None | None | N |
| T/C | 0.6737 | likely_pathogenic | 0.6997 | pathogenic | -0.439 | Destabilizing | 0.994 | D | 0.773 | deleterious | None | None | None | None | N |
| T/D | 0.6888 | likely_pathogenic | 0.7577 | pathogenic | -0.244 | Destabilizing | 0.959 | D | 0.71 | prob.delet. | None | None | None | None | N |
| T/E | 0.6163 | likely_pathogenic | 0.7078 | pathogenic | -0.149 | Destabilizing | 0.921 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/F | 0.5749 | likely_pathogenic | 0.6326 | pathogenic | -0.685 | Destabilizing | 0.979 | D | 0.792 | deleterious | None | None | None | None | N |
| T/G | 0.403 | ambiguous | 0.4142 | ambiguous | -1.166 | Destabilizing | 0.769 | D | 0.609 | neutral | None | None | None | None | N |
| T/H | 0.4543 | ambiguous | 0.5323 | ambiguous | -1.295 | Destabilizing | 0.994 | D | 0.784 | deleterious | None | None | None | None | N |
| T/I | 0.5047 | ambiguous | 0.524 | ambiguous | 0.026 | Stabilizing | 0.946 | D | 0.754 | deleterious | N | 0.471043297 | None | None | N |
| T/K | 0.4585 | ambiguous | 0.557 | ambiguous | -0.502 | Destabilizing | 0.921 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/L | 0.3056 | likely_benign | 0.3247 | benign | 0.026 | Stabilizing | 0.87 | D | 0.601 | neutral | None | None | None | None | N |
| T/M | 0.2156 | likely_benign | 0.2212 | benign | 0.049 | Stabilizing | 0.998 | D | 0.785 | deleterious | None | None | None | None | N |
| T/N | 0.2092 | likely_benign | 0.2261 | benign | -0.758 | Destabilizing | 0.898 | D | 0.681 | prob.neutral | N | 0.501493338 | None | None | N |
| T/P | 0.7012 | likely_pathogenic | 0.679 | pathogenic | -0.224 | Destabilizing | 0.946 | D | 0.756 | deleterious | N | 0.470789808 | None | None | N |
| T/Q | 0.3938 | ambiguous | 0.4662 | ambiguous | -0.688 | Destabilizing | 0.959 | D | 0.779 | deleterious | None | None | None | None | N |
| T/R | 0.3822 | ambiguous | 0.4919 | ambiguous | -0.478 | Destabilizing | 0.959 | D | 0.755 | deleterious | None | None | None | None | N |
| T/S | 0.1327 | likely_benign | 0.1394 | benign | -1.057 | Destabilizing | 0.016 | N | 0.463 | neutral | N | 0.432302612 | None | None | N |
| T/V | 0.3355 | likely_benign | 0.3588 | ambiguous | -0.224 | Destabilizing | 0.87 | D | 0.558 | neutral | None | None | None | None | N |
| T/W | 0.8816 | likely_pathogenic | 0.9161 | pathogenic | -0.735 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| T/Y | 0.5836 | likely_pathogenic | 0.6428 | pathogenic | -0.423 | Destabilizing | 0.979 | D | 0.796 | 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.