Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24823 | 74692;74693;74694 | chr2:178571665;178571664;178571663 | chr2:179436392;179436391;179436390 |
| N2AB | 23182 | 69769;69770;69771 | chr2:178571665;178571664;178571663 | chr2:179436392;179436391;179436390 |
| N2A | 22255 | 66988;66989;66990 | chr2:178571665;178571664;178571663 | chr2:179436392;179436391;179436390 |
| N2B | 15758 | 47497;47498;47499 | chr2:178571665;178571664;178571663 | chr2:179436392;179436391;179436390 |
| Novex-1 | 15883 | 47872;47873;47874 | chr2:178571665;178571664;178571663 | chr2:179436392;179436391;179436390 |
| Novex-2 | 15950 | 48073;48074;48075 | chr2:178571665;178571664;178571663 | chr2:179436392;179436391;179436390 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs368071644  |
-0.662 | 0.919 | N | 0.513 | 0.3 | None | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 1.29416E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/G | rs368071644 |
-0.662 | 0.919 | N | 0.513 | 0.3 | None | gnomAD-4.0.0 | 4.79045E-06 | None | None | None | None | N | None | 8.96915E-05 | 2.23644E-05 | None | 0 | 0 | None | 0 | 0 | 8.99591E-07 | 0 | 3.31422E-05 |
| A/T | None | None | 0.919 | N | 0.647 | 0.195 | 0.336647302497 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 3.66327E-05 |
| A/V | rs368071644 |
-0.403 | 0.958 | N | 0.723 | 0.33 | 0.41219620536 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| A/V | rs368071644 |
-0.403 | 0.958 | N | 0.723 | 0.33 | 0.41219620536 | gnomAD-4.0.0 | 2.05305E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69877E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5176 | ambiguous | 0.49 | ambiguous | -1.157 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| A/D | 0.7922 | likely_pathogenic | 0.7488 | pathogenic | -1.292 | Destabilizing | 0.988 | D | 0.74 | deleterious | N | 0.465897898 | None | None | N |
| A/E | 0.6104 | likely_pathogenic | 0.6025 | pathogenic | -1.367 | Destabilizing | 0.991 | D | 0.706 | prob.neutral | None | None | None | None | N |
| A/F | 0.7206 | likely_pathogenic | 0.6954 | pathogenic | -1.334 | Destabilizing | 0.995 | D | 0.783 | deleterious | None | None | None | None | N |
| A/G | 0.2951 | likely_benign | 0.2731 | benign | -1.101 | Destabilizing | 0.919 | D | 0.513 | neutral | N | 0.459241284 | None | None | N |
| A/H | 0.8299 | likely_pathogenic | 0.7983 | pathogenic | -1.104 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| A/I | 0.469 | ambiguous | 0.4654 | ambiguous | -0.621 | Destabilizing | 0.995 | D | 0.757 | deleterious | None | None | None | None | N |
| A/K | 0.8165 | likely_pathogenic | 0.8005 | pathogenic | -0.996 | Destabilizing | 0.991 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/L | 0.4377 | ambiguous | 0.4222 | ambiguous | -0.621 | Destabilizing | 0.968 | D | 0.698 | prob.neutral | None | None | None | None | N |
| A/M | 0.4315 | ambiguous | 0.4186 | ambiguous | -0.504 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/N | 0.585 | likely_pathogenic | 0.5201 | ambiguous | -0.786 | Destabilizing | 0.991 | D | 0.736 | prob.delet. | None | None | None | None | N |
| A/P | 0.5386 | ambiguous | 0.4873 | ambiguous | -0.687 | Destabilizing | 0.994 | D | 0.751 | deleterious | N | 0.487099889 | None | None | N |
| A/Q | 0.6592 | likely_pathogenic | 0.6377 | pathogenic | -1.069 | Destabilizing | 0.991 | D | 0.786 | deleterious | None | None | None | None | N |
| A/R | 0.7595 | likely_pathogenic | 0.7318 | pathogenic | -0.574 | Destabilizing | 0.991 | D | 0.771 | deleterious | None | None | None | None | N |
| A/S | 0.1157 | likely_benign | 0.1109 | benign | -1.115 | Destabilizing | 0.414 | N | 0.415 | neutral | N | 0.427838155 | None | None | N |
| A/T | 0.1843 | likely_benign | 0.1737 | benign | -1.108 | Destabilizing | 0.919 | D | 0.647 | neutral | N | 0.509630032 | None | None | N |
| A/V | 0.2273 | likely_benign | 0.2268 | benign | -0.687 | Destabilizing | 0.958 | D | 0.723 | prob.delet. | N | 0.509112744 | None | None | N |
| A/W | 0.9287 | likely_pathogenic | 0.9123 | pathogenic | -1.524 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| A/Y | 0.805 | likely_pathogenic | 0.7811 | pathogenic | -1.145 | Destabilizing | 1.0 | D | 0.778 | deleterious | 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.