Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30934 | 93025;93026;93027 | chr2:178548826;178548825;178548824 | chr2:179413553;179413552;179413551 |
| N2AB | 29293 | 88102;88103;88104 | chr2:178548826;178548825;178548824 | chr2:179413553;179413552;179413551 |
| N2A | 28366 | 85321;85322;85323 | chr2:178548826;178548825;178548824 | chr2:179413553;179413552;179413551 |
| N2B | 21869 | 65830;65831;65832 | chr2:178548826;178548825;178548824 | chr2:179413553;179413552;179413551 |
| Novex-1 | 21994 | 66205;66206;66207 | chr2:178548826;178548825;178548824 | chr2:179413553;179413552;179413551 |
| Novex-2 | 22061 | 66406;66407;66408 | chr2:178548826;178548825;178548824 | chr2:179413553;179413552;179413551 |
| 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/A | None | None | 0.865 | N | 0.411 | 0.194 | 0.143124449307 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| T/I | rs774501308  |
-0.424 | 0.957 | N | 0.612 | 0.303 | 0.325533332567 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65782E-04 |
| T/I | rs774501308 |
-0.424 | 0.957 | N | 0.612 | 0.303 | 0.325533332567 | gnomAD-4.0.0 | 1.36928E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52092E-05 | None | 1.906E-05 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1426 | likely_benign | 0.1461 | benign | -0.649 | Destabilizing | 0.865 | D | 0.411 | neutral | N | 0.491225125 | None | None | N |
| T/C | 0.5203 | ambiguous | 0.5117 | ambiguous | -0.296 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| T/D | 0.7825 | likely_pathogenic | 0.7803 | pathogenic | -0.284 | Destabilizing | 0.992 | D | 0.661 | neutral | None | None | None | None | N |
| T/E | 0.6847 | likely_pathogenic | 0.683 | pathogenic | -0.285 | Destabilizing | 0.992 | D | 0.631 | neutral | None | None | None | None | N |
| T/F | 0.3545 | ambiguous | 0.3636 | ambiguous | -0.611 | Destabilizing | 0.983 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/G | 0.4115 | ambiguous | 0.3975 | ambiguous | -0.917 | Destabilizing | 0.992 | D | 0.599 | neutral | None | None | None | None | N |
| T/H | 0.3952 | ambiguous | 0.3837 | ambiguous | -1.19 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/I | 0.1835 | likely_benign | 0.2087 | benign | -0.024 | Destabilizing | 0.957 | D | 0.612 | neutral | N | 0.461857406 | None | None | N |
| T/K | 0.5071 | ambiguous | 0.5313 | ambiguous | -0.837 | Destabilizing | 0.983 | D | 0.617 | neutral | None | None | None | None | N |
| T/L | 0.1297 | likely_benign | 0.1364 | benign | -0.024 | Destabilizing | 0.745 | D | 0.453 | neutral | None | None | None | None | N |
| T/M | 0.0827 | likely_benign | 0.0843 | benign | 0.219 | Stabilizing | 0.547 | D | 0.393 | neutral | None | None | None | None | N |
| T/N | 0.1759 | likely_benign | 0.1775 | benign | -0.655 | Destabilizing | 0.989 | D | 0.637 | neutral | N | 0.494089284 | None | None | N |
| T/P | 0.5042 | ambiguous | 0.5189 | ambiguous | -0.199 | Destabilizing | 0.996 | D | 0.659 | neutral | N | 0.509040094 | None | None | N |
| T/Q | 0.3673 | ambiguous | 0.3632 | ambiguous | -0.782 | Destabilizing | 0.992 | D | 0.671 | neutral | None | None | None | None | N |
| T/R | 0.4451 | ambiguous | 0.47 | ambiguous | -0.614 | Destabilizing | 0.983 | D | 0.661 | neutral | None | None | None | None | N |
| T/S | 0.174 | likely_benign | 0.174 | benign | -0.883 | Destabilizing | 0.928 | D | 0.419 | neutral | N | 0.468769552 | None | None | N |
| T/V | 0.1574 | likely_benign | 0.1652 | benign | -0.199 | Destabilizing | 0.895 | D | 0.397 | neutral | None | None | None | None | N |
| T/W | 0.7193 | likely_pathogenic | 0.739 | pathogenic | -0.601 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4099 | ambiguous | 0.4091 | ambiguous | -0.392 | Destabilizing | 0.992 | D | 0.696 | prob.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.