Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22719 | 68380;68381;68382 | chr2:178578875;178578874;178578873 | chr2:179443602;179443601;179443600 |
| N2AB | 21078 | 63457;63458;63459 | chr2:178578875;178578874;178578873 | chr2:179443602;179443601;179443600 |
| N2A | 20151 | 60676;60677;60678 | chr2:178578875;178578874;178578873 | chr2:179443602;179443601;179443600 |
| N2B | 13654 | 41185;41186;41187 | chr2:178578875;178578874;178578873 | chr2:179443602;179443601;179443600 |
| Novex-1 | 13779 | 41560;41561;41562 | chr2:178578875;178578874;178578873 | chr2:179443602;179443601;179443600 |
| Novex-2 | 13846 | 41761;41762;41763 | chr2:178578875;178578874;178578873 | chr2:179443602;179443601;179443600 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs2047057436  |
None | 0.166 | N | 0.637 | 0.215 | 0.18274738541 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93648E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs2047057436 |
None | 0.166 | N | 0.637 | 0.215 | 0.18274738541 | gnomAD-4.0.0 | 3.04496E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 3.41142E-04 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | rs1291771757 |
-1.291 | 0.491 | N | 0.701 | 0.175 | 0.186928172975 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/N | rs1291771757 |
-1.291 | 0.491 | N | 0.701 | 0.175 | 0.186928172975 | gnomAD-4.0.0 | 3.18495E-06 | None | None | None | None | N | None | 0 | 4.57415E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | None | None | 0.003 | N | 0.631 | 0.296 | 0.208000267992 | gnomAD-4.0.0 | 1.59247E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77701E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1173 | likely_benign | 0.1113 | benign | -1.221 | Destabilizing | 0.002 | N | 0.302 | neutral | None | None | None | None | N |
| S/C | 0.0707 | likely_benign | 0.0714 | benign | -1.104 | Destabilizing | 0.007 | N | 0.637 | neutral | N | 0.47684561 | None | None | N |
| S/D | 0.859 | likely_pathogenic | 0.8721 | pathogenic | -2.06 | Highly Destabilizing | 0.722 | D | 0.68 | prob.neutral | None | None | None | None | N |
| S/E | 0.8238 | likely_pathogenic | 0.8375 | pathogenic | -1.845 | Destabilizing | 0.561 | D | 0.687 | prob.neutral | None | None | None | None | N |
| S/F | 0.2463 | likely_benign | 0.2636 | benign | -0.871 | Destabilizing | 0.002 | N | 0.529 | neutral | None | None | None | None | N |
| S/G | 0.1799 | likely_benign | 0.1619 | benign | -1.6 | Destabilizing | 0.166 | N | 0.637 | neutral | N | 0.483877179 | None | None | N |
| S/H | 0.4293 | ambiguous | 0.472 | ambiguous | -1.739 | Destabilizing | 0.901 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/I | 0.3125 | likely_benign | 0.3264 | benign | -0.246 | Destabilizing | 0.491 | N | 0.705 | prob.neutral | N | 0.47822969 | None | None | N |
| S/K | 0.7904 | likely_pathogenic | 0.8028 | pathogenic | -0.652 | Destabilizing | 0.39 | N | 0.664 | neutral | None | None | None | None | N |
| S/L | 0.1421 | likely_benign | 0.1377 | benign | -0.246 | Destabilizing | 0.209 | N | 0.707 | prob.neutral | None | None | None | None | N |
| S/M | 0.2166 | likely_benign | 0.203 | benign | -0.486 | Destabilizing | 0.965 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/N | 0.3238 | likely_benign | 0.3379 | benign | -1.388 | Destabilizing | 0.491 | N | 0.701 | prob.neutral | N | 0.4833702 | None | None | N |
| S/P | 0.9897 | likely_pathogenic | 0.9911 | pathogenic | -0.54 | Destabilizing | 0.901 | D | 0.763 | deleterious | None | None | None | None | N |
| S/Q | 0.5826 | likely_pathogenic | 0.5786 | pathogenic | -1.117 | Destabilizing | 0.818 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/R | 0.6344 | likely_pathogenic | 0.6341 | pathogenic | -0.952 | Destabilizing | 0.003 | N | 0.631 | neutral | N | 0.43778579 | None | None | N |
| S/T | 0.1235 | likely_benign | 0.1396 | benign | -1.029 | Destabilizing | 0.285 | N | 0.619 | neutral | N | 0.482115357 | None | None | N |
| S/V | 0.2948 | likely_benign | 0.3136 | benign | -0.54 | Destabilizing | 0.39 | N | 0.718 | prob.delet. | None | None | None | None | N |
| S/W | 0.3755 | ambiguous | 0.4263 | ambiguous | -1.151 | Destabilizing | 0.991 | D | 0.749 | deleterious | None | None | None | None | N |
| S/Y | 0.223 | likely_benign | 0.2648 | benign | -0.737 | Destabilizing | 0.692 | D | 0.735 | 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.