Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32003 | 96232;96233;96234 | chr2:178544222;178544221;178544220 | chr2:179408949;179408948;179408947 |
| N2AB | 30362 | 91309;91310;91311 | chr2:178544222;178544221;178544220 | chr2:179408949;179408948;179408947 |
| N2A | 29435 | 88528;88529;88530 | chr2:178544222;178544221;178544220 | chr2:179408949;179408948;179408947 |
| N2B | 22938 | 69037;69038;69039 | chr2:178544222;178544221;178544220 | chr2:179408949;179408948;179408947 |
| Novex-1 | 23063 | 69412;69413;69414 | chr2:178544222;178544221;178544220 | chr2:179408949;179408948;179408947 |
| Novex-2 | 23130 | 69613;69614;69615 | chr2:178544222;178544221;178544220 | chr2:179408949;179408948;179408947 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs745962752  |
None | 0.974 | N | 0.698 | 0.365 | 0.841138462312 | gnomAD-4.0.0 | 2.1219E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69969E-05 | 0 | 1.65706E-05 |
| I/T | rs745962752 |
-2.294 | 0.067 | N | 0.243 | 0.234 | 0.590021811661 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.93748E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs745962752 |
-2.294 | 0.067 | N | 0.243 | 0.234 | 0.590021811661 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs745962752 |
-2.294 | 0.067 | N | 0.243 | 0.234 | 0.590021811661 | gnomAD-4.0.0 | 2.66564E-05 | None | None | None | None | N | None | 6.6761E-05 | 0 | None | 0 | 7.3536E-04 | None | 0 | 0 | 3.39197E-06 | 0 | 1.60159E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1591 | likely_benign | 0.1595 | benign | -2.221 | Highly Destabilizing | 0.038 | N | 0.273 | neutral | None | None | None | None | N |
| I/C | 0.5981 | likely_pathogenic | 0.6109 | pathogenic | -1.438 | Destabilizing | 0.994 | D | 0.526 | neutral | None | None | None | None | N |
| I/D | 0.6968 | likely_pathogenic | 0.7055 | pathogenic | -2.44 | Highly Destabilizing | 0.981 | D | 0.68 | prob.neutral | None | None | None | None | N |
| I/E | 0.4694 | ambiguous | 0.4813 | ambiguous | -2.204 | Highly Destabilizing | 0.935 | D | 0.652 | prob.neutral | None | None | None | None | N |
| I/F | 0.163 | likely_benign | 0.1635 | benign | -1.314 | Destabilizing | 0.974 | D | 0.485 | neutral | N | 0.491786138 | None | None | N |
| I/G | 0.5682 | likely_pathogenic | 0.5882 | pathogenic | -2.759 | Highly Destabilizing | 0.876 | D | 0.614 | neutral | None | None | None | None | N |
| I/H | 0.4664 | ambiguous | 0.4843 | ambiguous | -2.12 | Highly Destabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | N |
| I/K | 0.2929 | likely_benign | 0.3182 | benign | -1.714 | Destabilizing | 0.876 | D | 0.659 | prob.neutral | None | None | None | None | N |
| I/L | 0.126 | likely_benign | 0.1338 | benign | -0.671 | Destabilizing | 0.325 | N | 0.305 | neutral | N | 0.49561309 | None | None | N |
| I/M | 0.0754 | likely_benign | 0.0786 | benign | -0.58 | Destabilizing | 0.974 | D | 0.476 | neutral | N | 0.486587702 | None | None | N |
| I/N | 0.2905 | likely_benign | 0.2872 | benign | -2.118 | Highly Destabilizing | 0.974 | D | 0.698 | prob.delet. | N | 0.498957965 | None | None | N |
| I/P | 0.7885 | likely_pathogenic | 0.7757 | pathogenic | -1.168 | Destabilizing | 0.981 | D | 0.676 | prob.neutral | None | None | None | None | N |
| I/Q | 0.3495 | ambiguous | 0.3696 | ambiguous | -1.956 | Destabilizing | 0.994 | D | 0.697 | prob.delet. | None | None | None | None | N |
| I/R | 0.2352 | likely_benign | 0.2449 | benign | -1.485 | Destabilizing | 0.981 | D | 0.689 | prob.delet. | None | None | None | None | N |
| I/S | 0.2222 | likely_benign | 0.2195 | benign | -2.8 | Highly Destabilizing | 0.728 | D | 0.536 | neutral | N | 0.487094681 | None | None | N |
| I/T | 0.0771 | likely_benign | 0.0731 | benign | -2.407 | Highly Destabilizing | 0.067 | N | 0.243 | neutral | N | 0.482299863 | None | None | N |
| I/V | 0.0735 | likely_benign | 0.0764 | benign | -1.168 | Destabilizing | 0.029 | N | 0.151 | neutral | N | 0.388098836 | None | None | N |
| I/W | 0.6886 | likely_pathogenic | 0.6973 | pathogenic | -1.671 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | N |
| I/Y | 0.4817 | ambiguous | 0.4781 | ambiguous | -1.329 | Destabilizing | 0.994 | D | 0.539 | 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.