Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16027 | 48304;48305;48306 | chr2:178616810;178616809;178616808 | chr2:179481537;179481536;179481535 |
| N2AB | 14386 | 43381;43382;43383 | chr2:178616810;178616809;178616808 | chr2:179481537;179481536;179481535 |
| N2A | 13459 | 40600;40601;40602 | chr2:178616810;178616809;178616808 | chr2:179481537;179481536;179481535 |
| N2B | 6962 | 21109;21110;21111 | chr2:178616810;178616809;178616808 | chr2:179481537;179481536;179481535 |
| Novex-1 | 7087 | 21484;21485;21486 | chr2:178616810;178616809;178616808 | chr2:179481537;179481536;179481535 |
| Novex-2 | 7154 | 21685;21686;21687 | chr2:178616810;178616809;178616808 | chr2:179481537;179481536;179481535 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs765032242  |
0.028 | 1.0 | D | 0.767 | 0.456 | 0.520002024791 | gnomAD-2.1.1 | 2.87E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 3.93E-05 | 0 |
| R/C | rs765032242 |
0.028 | 1.0 | D | 0.767 | 0.456 | 0.520002024791 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| R/C | rs765032242 |
0.028 | 1.0 | D | 0.767 | 0.456 | 0.520002024791 | gnomAD-4.0.0 | 1.42637E-05 | None | None | None | None | N | None | 1.33715E-05 | 3.33957E-05 | None | 0 | 0 | None | 0 | 0 | 1.44172E-05 | 3.29525E-05 | 0 |
| R/H | rs757013471 |
-0.699 | 1.0 | D | 0.751 | 0.453 | 0.296329037015 | gnomAD-2.1.1 | 5.73E-05 | None | None | None | None | N | None | 4.14E-05 | 8.5E-05 | None | 0 | 0 | None | 3.59524E-04 | None | 0 | 7.86E-06 | 0 |
| R/H | rs757013471 |
-0.699 | 1.0 | D | 0.751 | 0.453 | 0.296329037015 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs757013471 |
-0.699 | 1.0 | D | 0.751 | 0.453 | 0.296329037015 | gnomAD-4.0.0 | 1.86038E-05 | None | None | None | None | N | None | 2.67315E-05 | 5.00818E-05 | None | 0 | 0 | None | 0 | 0 | 2.54416E-06 | 2.30632E-04 | 1.60272E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8389 | likely_pathogenic | 0.8646 | pathogenic | -0.101 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| R/C | 0.5134 | ambiguous | 0.5845 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.767 | deleterious | D | 0.610448983 | None | None | N |
| R/D | 0.9209 | likely_pathogenic | 0.9308 | pathogenic | -0.003 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/E | 0.7239 | likely_pathogenic | 0.7474 | pathogenic | 0.089 | Stabilizing | 0.999 | D | 0.616 | neutral | None | None | None | None | N |
| R/F | 0.844 | likely_pathogenic | 0.8755 | pathogenic | -0.161 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| R/G | 0.7678 | likely_pathogenic | 0.7991 | pathogenic | -0.346 | Destabilizing | 1.0 | D | 0.573 | neutral | D | 0.570705029 | None | None | N |
| R/H | 0.2933 | likely_benign | 0.352 | ambiguous | -0.807 | Destabilizing | 1.0 | D | 0.751 | deleterious | D | 0.570705029 | None | None | N |
| R/I | 0.5538 | ambiguous | 0.5944 | pathogenic | 0.523 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| R/K | 0.2925 | likely_benign | 0.3219 | benign | -0.169 | Destabilizing | 0.998 | D | 0.501 | neutral | None | None | None | None | N |
| R/L | 0.5878 | likely_pathogenic | 0.6274 | pathogenic | 0.523 | Stabilizing | 1.0 | D | 0.573 | neutral | D | 0.557286812 | None | None | N |
| R/M | 0.7139 | likely_pathogenic | 0.7493 | pathogenic | 0.028 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/N | 0.8879 | likely_pathogenic | 0.9104 | pathogenic | 0.103 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| R/P | 0.7358 | likely_pathogenic | 0.7697 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | D | 0.536653701 | None | None | N |
| R/Q | 0.3202 | likely_benign | 0.3652 | ambiguous | 0.018 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| R/S | 0.9047 | likely_pathogenic | 0.9249 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.628 | neutral | D | 0.566243509 | None | None | N |
| R/T | 0.7783 | likely_pathogenic | 0.8139 | pathogenic | -0.089 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| R/V | 0.719 | likely_pathogenic | 0.7568 | pathogenic | 0.337 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/W | 0.4293 | ambiguous | 0.4948 | ambiguous | -0.115 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| R/Y | 0.6733 | likely_pathogenic | 0.7392 | pathogenic | 0.266 | Stabilizing | 1.0 | D | 0.714 | 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.