Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21011 | 63256;63257;63258 | chr2:178588694;178588693;178588692 | chr2:179453421;179453420;179453419 |
| N2AB | 19370 | 58333;58334;58335 | chr2:178588694;178588693;178588692 | chr2:179453421;179453420;179453419 |
| N2A | 18443 | 55552;55553;55554 | chr2:178588694;178588693;178588692 | chr2:179453421;179453420;179453419 |
| N2B | 11946 | 36061;36062;36063 | chr2:178588694;178588693;178588692 | chr2:179453421;179453420;179453419 |
| Novex-1 | 12071 | 36436;36437;36438 | chr2:178588694;178588693;178588692 | chr2:179453421;179453420;179453419 |
| Novex-2 | 12138 | 36637;36638;36639 | chr2:178588694;178588693;178588692 | chr2:179453421;179453420;179453419 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | rs1553639384  |
None | 1.0 | N | 0.761 | 0.487 | 0.787965464792 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 0 |
| V/F | rs758606539 |
-0.681 | 1.0 | N | 0.702 | 0.379 | 0.710150875617 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs758606539 |
-0.681 | 1.0 | N | 0.702 | 0.379 | 0.710150875617 | gnomAD-4.0.0 | 1.59243E-06 | None | None | None | None | N | None | 0 | 2.28739E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | None | -0.094 | 0.997 | N | 0.482 | 0.254 | 0.516106911764 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| V/L | rs758606539 |
None | 0.997 | N | 0.541 | 0.305 | 0.617063767924 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs758606539 |
None | 0.997 | N | 0.541 | 0.305 | 0.617063767924 | gnomAD-4.0.0 | 2.56417E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78962E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2025 | likely_benign | 0.199 | benign | -1.127 | Destabilizing | 0.999 | D | 0.552 | neutral | N | 0.449659009 | None | None | N |
| V/C | 0.5927 | likely_pathogenic | 0.6119 | pathogenic | -0.716 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| V/D | 0.5843 | likely_pathogenic | 0.5583 | ambiguous | -0.924 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.484830375 | None | None | N |
| V/E | 0.4546 | ambiguous | 0.4228 | ambiguous | -0.948 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/F | 0.1659 | likely_benign | 0.1744 | benign | -0.858 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | N | 0.467130049 | None | None | N |
| V/G | 0.2328 | likely_benign | 0.2265 | benign | -1.397 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | N | 0.513806488 | None | None | N |
| V/H | 0.5325 | ambiguous | 0.5314 | ambiguous | -0.881 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| V/I | 0.0732 | likely_benign | 0.0711 | benign | -0.505 | Destabilizing | 0.997 | D | 0.482 | neutral | N | 0.462126874 | None | None | N |
| V/K | 0.5207 | ambiguous | 0.5113 | ambiguous | -1.023 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| V/L | 0.1769 | likely_benign | 0.1731 | benign | -0.505 | Destabilizing | 0.997 | D | 0.541 | neutral | N | 0.452256597 | None | None | N |
| V/M | 0.1282 | likely_benign | 0.128 | benign | -0.434 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/N | 0.2459 | likely_benign | 0.2367 | benign | -0.804 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| V/P | 0.9502 | likely_pathogenic | 0.9329 | pathogenic | -0.677 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| V/Q | 0.3302 | likely_benign | 0.3158 | benign | -0.983 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| V/R | 0.5203 | ambiguous | 0.5186 | ambiguous | -0.472 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| V/S | 0.1907 | likely_benign | 0.1813 | benign | -1.253 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/T | 0.1804 | likely_benign | 0.1788 | benign | -1.174 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| V/W | 0.8095 | likely_pathogenic | 0.8084 | pathogenic | -1.032 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| V/Y | 0.462 | ambiguous | 0.4453 | ambiguous | -0.744 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | 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.