Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33223 | 99892;99893;99894 | chr2:178537540;178537539;178537538 | chr2:179402267;179402266;179402265 |
| N2AB | 31582 | 94969;94970;94971 | chr2:178537540;178537539;178537538 | chr2:179402267;179402266;179402265 |
| N2A | 30655 | 92188;92189;92190 | chr2:178537540;178537539;178537538 | chr2:179402267;179402266;179402265 |
| N2B | 24158 | 72697;72698;72699 | chr2:178537540;178537539;178537538 | chr2:179402267;179402266;179402265 |
| Novex-1 | 24283 | 73072;73073;73074 | chr2:178537540;178537539;178537538 | chr2:179402267;179402266;179402265 |
| Novex-2 | 24350 | 73273;73274;73275 | chr2:178537540;178537539;178537538 | chr2:179402267;179402266;179402265 |
| 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 | rs1367376217  |
-1.861 | 1.0 | N | 0.762 | 0.515 | 0.822579953997 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.56E-05 | 0 |
| R/C | rs1367376217 |
-1.861 | 1.0 | N | 0.762 | 0.515 | 0.822579953997 | 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 |
| R/C | rs1367376217 |
-1.861 | 1.0 | N | 0.762 | 0.515 | 0.822579953997 | gnomAD-4.0.0 | 2.47908E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69528E-06 | 1.09842E-05 | 1.60164E-05 |
| R/H | rs369081242 |
-2.104 | 1.0 | N | 0.752 | 0.465 | None | gnomAD-2.1.1 | 8.04E-05 | None | None | None | None | N | None | 1.93874E-04 | 8.7E-05 | None | 0 | 6.13497E-04 | None | 3.27E-05 | None | 0 | 1.77E-05 | 0 |
| R/H | rs369081242 |
-2.104 | 1.0 | N | 0.752 | 0.465 | None | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | N | None | 2.65572E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs369081242 |
-2.104 | 1.0 | N | 0.752 | 0.465 | None | gnomAD-4.0.0 | 4.39996E-05 | None | None | None | None | N | None | 2.79985E-04 | 5.0005E-05 | None | 0 | 4.45951E-05 | None | 0 | 0 | 2.79722E-05 | 2.19645E-05 | 1.60087E-04 |
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 | 0.9314 | likely_pathogenic | 0.9246 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| R/C | 0.5482 | ambiguous | 0.5785 | pathogenic | -0.158 | Destabilizing | 1.0 | D | 0.762 | deleterious | N | 0.483415059 | None | None | N |
| R/D | 0.9713 | likely_pathogenic | 0.9595 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/E | 0.8332 | likely_pathogenic | 0.8046 | pathogenic | 0.044 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/F | 0.9307 | likely_pathogenic | 0.9212 | pathogenic | 0.053 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/G | 0.8958 | likely_pathogenic | 0.8931 | pathogenic | -0.306 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.494682459 | None | None | N |
| R/H | 0.3383 | likely_benign | 0.2914 | benign | -0.875 | Destabilizing | 1.0 | D | 0.752 | deleterious | N | 0.512894916 | None | None | N |
| R/I | 0.8046 | likely_pathogenic | 0.761 | pathogenic | 0.693 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/K | 0.331 | likely_benign | 0.2762 | benign | -0.092 | Destabilizing | 1.0 | D | 0.493 | neutral | None | None | None | None | N |
| R/L | 0.7467 | likely_pathogenic | 0.7178 | pathogenic | 0.693 | Stabilizing | 1.0 | D | 0.657 | neutral | N | 0.518474094 | None | None | N |
| R/M | 0.8481 | likely_pathogenic | 0.8202 | pathogenic | 0.046 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/N | 0.9188 | likely_pathogenic | 0.8994 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| R/P | 0.9905 | likely_pathogenic | 0.9855 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.494935948 | None | None | N |
| R/Q | 0.3195 | likely_benign | 0.2907 | benign | 0.078 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/S | 0.9125 | likely_pathogenic | 0.9003 | pathogenic | -0.288 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.498674825 | None | None | N |
| R/T | 0.8688 | likely_pathogenic | 0.8216 | pathogenic | 0.004 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/V | 0.8592 | likely_pathogenic | 0.8378 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/W | 0.6488 | likely_pathogenic | 0.6029 | pathogenic | 0.084 | Stabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/Y | 0.8104 | likely_pathogenic | 0.7915 | pathogenic | 0.449 | Stabilizing | 1.0 | D | 0.741 | 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.