Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9213 | 27862;27863;27864 | chr2:178712193;178712192;178712191 | chr2:179576920;179576919;179576918 |
| N2AB | 8896 | 26911;26912;26913 | chr2:178712193;178712192;178712191 | chr2:179576920;179576919;179576918 |
| N2A | 7969 | 24130;24131;24132 | chr2:178712193;178712192;178712191 | chr2:179576920;179576919;179576918 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs747751433  |
0.006 | 1.0 | N | 0.681 | 0.365 | 0.436132833422 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | I | None | 4.14E-05 | 5.67E-05 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 1.57E-05 | 0 |
| P/L | rs747751433 |
0.006 | 1.0 | N | 0.681 | 0.365 | 0.436132833422 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs747751433 |
0.006 | 1.0 | N | 0.681 | 0.365 | 0.436132833422 | gnomAD-4.0.0 | 1.05374E-05 | None | None | None | None | I | None | 4.00684E-05 | 3.33645E-05 | None | 0 | 0 | None | 0 | 0 | 6.78193E-06 | 2.19713E-05 | 3.20266E-05 |
| P/T | None | None | 0.999 | N | 0.679 | 0.327 | 0.277317399466 | gnomAD-4.0.0 | 6.8436E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99638E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0738 | likely_benign | 0.0772 | benign | -0.456 | Destabilizing | 0.992 | D | 0.485 | neutral | N | 0.476583746 | None | None | I |
| P/C | 0.5898 | likely_pathogenic | 0.6392 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| P/D | 0.318 | likely_benign | 0.3329 | benign | -0.398 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/E | 0.2315 | likely_benign | 0.2439 | benign | -0.508 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/F | 0.5257 | ambiguous | 0.5619 | ambiguous | -0.648 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| P/G | 0.3142 | likely_benign | 0.3303 | benign | -0.592 | Destabilizing | 0.997 | D | 0.634 | neutral | None | None | None | None | I |
| P/H | 0.1973 | likely_benign | 0.2016 | benign | -0.176 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | I |
| P/I | 0.3741 | ambiguous | 0.4071 | ambiguous | -0.246 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| P/K | 0.2973 | likely_benign | 0.3127 | benign | -0.493 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | I |
| P/L | 0.1424 | likely_benign | 0.1477 | benign | -0.246 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.499652607 | None | None | I |
| P/M | 0.317 | likely_benign | 0.3598 | ambiguous | -0.364 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | I |
| P/N | 0.255 | likely_benign | 0.2715 | benign | -0.214 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | I |
| P/Q | 0.1602 | likely_benign | 0.1641 | benign | -0.456 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | N | 0.503058271 | None | None | I |
| P/R | 0.186 | likely_benign | 0.1862 | benign | 0.029 | Stabilizing | 1.0 | D | 0.672 | neutral | N | 0.506925296 | None | None | I |
| P/S | 0.1185 | likely_benign | 0.1255 | benign | -0.543 | Destabilizing | 0.957 | D | 0.359 | neutral | N | 0.430328594 | None | None | I |
| P/T | 0.1018 | likely_benign | 0.1109 | benign | -0.555 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | N | 0.502018121 | None | None | I |
| P/V | 0.2406 | likely_benign | 0.2613 | benign | -0.281 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | I |
| P/W | 0.6812 | likely_pathogenic | 0.696 | pathogenic | -0.741 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/Y | 0.4614 | ambiguous | 0.4833 | ambiguous | -0.447 | Destabilizing | 1.0 | D | 0.663 | 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.