Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25280 | 76063;76064;76065 | chr2:178570294;178570293;178570292 | chr2:179435021;179435020;179435019 |
| N2AB | 23639 | 71140;71141;71142 | chr2:178570294;178570293;178570292 | chr2:179435021;179435020;179435019 |
| N2A | 22712 | 68359;68360;68361 | chr2:178570294;178570293;178570292 | chr2:179435021;179435020;179435019 |
| N2B | 16215 | 48868;48869;48870 | chr2:178570294;178570293;178570292 | chr2:179435021;179435020;179435019 |
| Novex-1 | 16340 | 49243;49244;49245 | chr2:178570294;178570293;178570292 | chr2:179435021;179435020;179435019 |
| Novex-2 | 16407 | 49444;49445;49446 | chr2:178570294;178570293;178570292 | chr2:179435021;179435020;179435019 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs780403765  |
None | 0.002 | N | 0.224 | 0.2 | 0.48512917806 | gnomAD-4.0.0 | 1.43724E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.88913E-05 | 0 | 0 |
| M/V | rs878918988 |
-1.205 | 0.08 | N | 0.478 | 0.205 | 0.474954162714 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| M/V | rs878918988 |
-1.205 | 0.08 | N | 0.478 | 0.205 | 0.474954162714 | gnomAD-4.0.0 | 9.58149E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25942E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3988 | ambiguous | 0.4493 | ambiguous | -2.586 | Highly Destabilizing | 0.345 | N | 0.563 | neutral | None | None | None | None | N |
| M/C | 0.5427 | ambiguous | 0.6031 | pathogenic | -2.439 | Highly Destabilizing | 0.965 | D | 0.631 | neutral | None | None | None | None | N |
| M/D | 0.95 | likely_pathogenic | 0.9635 | pathogenic | -2.417 | Highly Destabilizing | 0.722 | D | 0.655 | neutral | None | None | None | None | N |
| M/E | 0.7356 | likely_pathogenic | 0.7713 | pathogenic | -2.233 | Highly Destabilizing | 0.561 | D | 0.628 | neutral | None | None | None | None | N |
| M/F | 0.4733 | ambiguous | 0.514 | ambiguous | -1.019 | Destabilizing | 0.722 | D | 0.587 | neutral | None | None | None | None | N |
| M/G | 0.6944 | likely_pathogenic | 0.7639 | pathogenic | -3.0 | Highly Destabilizing | 0.561 | D | 0.641 | neutral | None | None | None | None | N |
| M/H | 0.5615 | ambiguous | 0.633 | pathogenic | -2.466 | Highly Destabilizing | 0.901 | D | 0.609 | neutral | None | None | None | None | N |
| M/I | 0.5629 | ambiguous | 0.5775 | pathogenic | -1.399 | Destabilizing | 0.002 | N | 0.224 | neutral | N | 0.455544831 | None | None | N |
| M/K | 0.2194 | likely_benign | 0.2802 | benign | -1.849 | Destabilizing | 0.166 | N | 0.623 | neutral | N | 0.455678117 | None | None | N |
| M/L | 0.1964 | likely_benign | 0.2114 | benign | -1.399 | Destabilizing | 0.036 | N | 0.332 | neutral | N | 0.457256985 | None | None | N |
| M/N | 0.6641 | likely_pathogenic | 0.7207 | pathogenic | -2.055 | Highly Destabilizing | 0.561 | D | 0.639 | neutral | None | None | None | None | N |
| M/P | 0.9918 | likely_pathogenic | 0.9953 | pathogenic | -1.779 | Destabilizing | 0.965 | D | 0.631 | neutral | None | None | None | None | N |
| M/Q | 0.27 | likely_benign | 0.3236 | benign | -1.857 | Destabilizing | 0.561 | D | 0.596 | neutral | None | None | None | None | N |
| M/R | 0.1914 | likely_benign | 0.2499 | benign | -1.693 | Destabilizing | 0.003 | N | 0.387 | neutral | N | 0.376582615 | None | None | N |
| M/S | 0.3366 | likely_benign | 0.3815 | ambiguous | -2.613 | Highly Destabilizing | 0.561 | D | 0.631 | neutral | None | None | None | None | N |
| M/T | 0.1705 | likely_benign | 0.1966 | benign | -2.329 | Highly Destabilizing | 0.285 | N | 0.621 | neutral | N | 0.438689867 | None | None | N |
| M/V | 0.1359 | likely_benign | 0.1454 | benign | -1.779 | Destabilizing | 0.08 | N | 0.478 | neutral | N | 0.438593866 | None | None | N |
| M/W | 0.7946 | likely_pathogenic | 0.8343 | pathogenic | -1.302 | Destabilizing | 0.991 | D | 0.627 | neutral | None | None | None | None | N |
| M/Y | 0.7327 | likely_pathogenic | 0.7701 | pathogenic | -1.355 | Destabilizing | 0.965 | D | 0.647 | neutral | 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.