Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27946 | 84061;84062;84063 | chr2:178562296;178562295;178562294 | chr2:179427023;179427022;179427021 |
| N2AB | 26305 | 79138;79139;79140 | chr2:178562296;178562295;178562294 | chr2:179427023;179427022;179427021 |
| N2A | 25378 | 76357;76358;76359 | chr2:178562296;178562295;178562294 | chr2:179427023;179427022;179427021 |
| N2B | 18881 | 56866;56867;56868 | chr2:178562296;178562295;178562294 | chr2:179427023;179427022;179427021 |
| Novex-1 | 19006 | 57241;57242;57243 | chr2:178562296;178562295;178562294 | chr2:179427023;179427022;179427021 |
| Novex-2 | 19073 | 57442;57443;57444 | chr2:178562296;178562295;178562294 | chr2:179427023;179427022;179427021 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1360228493  |
None | 1.0 | N | 0.628 | 0.39 | 0.368369118721 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85802E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1360228493 |
None | 1.0 | N | 0.628 | 0.39 | 0.368369118721 | gnomAD-4.0.0 | 3.84475E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.85555E-05 | None | 0 | 0 | 2.39367E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2073 | likely_benign | 0.2767 | benign | -0.182 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | N | 0.521884466 | None | None | N |
| D/C | 0.761 | likely_pathogenic | 0.8375 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/E | 0.1523 | likely_benign | 0.19 | benign | -0.317 | Destabilizing | 0.999 | D | 0.519 | neutral | N | 0.434822842 | None | None | N |
| D/F | 0.6191 | likely_pathogenic | 0.7318 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/G | 0.3632 | ambiguous | 0.4711 | ambiguous | -0.351 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.470315147 | None | None | N |
| D/H | 0.4289 | ambiguous | 0.5391 | ambiguous | -0.082 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.48788965 | None | None | N |
| D/I | 0.339 | likely_benign | 0.4536 | ambiguous | 0.206 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| D/K | 0.4792 | ambiguous | 0.6007 | pathogenic | 0.397 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/L | 0.3707 | ambiguous | 0.4724 | ambiguous | 0.206 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/M | 0.5943 | likely_pathogenic | 0.7006 | pathogenic | 0.339 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/N | 0.1575 | likely_benign | 0.2054 | benign | 0.204 | Stabilizing | 1.0 | D | 0.628 | neutral | N | 0.482876447 | None | None | N |
| D/P | 0.6298 | likely_pathogenic | 0.6944 | pathogenic | 0.099 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | N |
| D/Q | 0.4062 | ambiguous | 0.5144 | ambiguous | 0.205 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| D/R | 0.5585 | ambiguous | 0.6691 | pathogenic | 0.519 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| D/S | 0.1805 | likely_benign | 0.2322 | benign | 0.094 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/T | 0.3246 | likely_benign | 0.4272 | ambiguous | 0.22 | Stabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/V | 0.2077 | likely_benign | 0.2874 | benign | 0.099 | Stabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.478672939 | None | None | N |
| D/W | 0.9267 | likely_pathogenic | 0.9557 | pathogenic | -0.198 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2855 | likely_benign | 0.3848 | ambiguous | -0.044 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.511780803 | 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.