Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20891 | 62896;62897;62898 | chr2:178589054;178589053;178589052 | chr2:179453781;179453780;179453779 |
| N2AB | 19250 | 57973;57974;57975 | chr2:178589054;178589053;178589052 | chr2:179453781;179453780;179453779 |
| N2A | 18323 | 55192;55193;55194 | chr2:178589054;178589053;178589052 | chr2:179453781;179453780;179453779 |
| N2B | 11826 | 35701;35702;35703 | chr2:178589054;178589053;178589052 | chr2:179453781;179453780;179453779 |
| Novex-1 | 11951 | 36076;36077;36078 | chr2:178589054;178589053;178589052 | chr2:179453781;179453780;179453779 |
| Novex-2 | 12018 | 36277;36278;36279 | chr2:178589054;178589053;178589052 | chr2:179453781;179453780;179453779 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs770046598  |
-0.51 | 0.989 | N | 0.546 | 0.528 | 0.419835214384 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs770046598 |
-0.51 | 0.989 | N | 0.546 | 0.528 | 0.419835214384 | gnomAD-4.0.0 | 2.05875E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47842E-05 | 0 |
| D/N | rs2049675533 |
None | 0.733 | N | 0.197 | 0.168 | 0.321393169273 | gnomAD-4.0.0 | 3.20478E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71945E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7921 | likely_pathogenic | 0.7691 | pathogenic | -0.094 | Destabilizing | 0.989 | D | 0.583 | neutral | N | 0.493880812 | None | None | N |
| D/C | 0.9614 | likely_pathogenic | 0.959 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/E | 0.7585 | likely_pathogenic | 0.7248 | pathogenic | -0.63 | Destabilizing | 0.543 | D | 0.209 | neutral | N | 0.489246003 | None | None | N |
| D/F | 0.9759 | likely_pathogenic | 0.9703 | pathogenic | -0.433 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/G | 0.7828 | likely_pathogenic | 0.7469 | pathogenic | -0.336 | Destabilizing | 0.989 | D | 0.546 | neutral | N | 0.503137204 | None | None | N |
| D/H | 0.8724 | likely_pathogenic | 0.866 | pathogenic | -0.81 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | N | 0.490855846 | None | None | N |
| D/I | 0.9376 | likely_pathogenic | 0.9418 | pathogenic | 0.498 | Stabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/K | 0.9412 | likely_pathogenic | 0.9418 | pathogenic | 0.112 | Stabilizing | 0.992 | D | 0.581 | neutral | None | None | None | None | N |
| D/L | 0.939 | likely_pathogenic | 0.9333 | pathogenic | 0.498 | Stabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| D/M | 0.9661 | likely_pathogenic | 0.9655 | pathogenic | 0.918 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/N | 0.1917 | likely_benign | 0.1671 | benign | -0.085 | Destabilizing | 0.733 | D | 0.197 | neutral | N | 0.485331807 | None | None | N |
| D/P | 0.9774 | likely_pathogenic | 0.9711 | pathogenic | 0.325 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/Q | 0.9215 | likely_pathogenic | 0.9193 | pathogenic | -0.034 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| D/R | 0.9491 | likely_pathogenic | 0.9489 | pathogenic | -0.007 | Destabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/S | 0.4175 | ambiguous | 0.3851 | ambiguous | -0.216 | Destabilizing | 0.992 | D | 0.538 | neutral | None | None | None | None | N |
| D/T | 0.6091 | likely_pathogenic | 0.5829 | pathogenic | -0.03 | Destabilizing | 0.998 | D | 0.583 | neutral | None | None | None | None | N |
| D/V | 0.8673 | likely_pathogenic | 0.8728 | pathogenic | 0.325 | Stabilizing | 0.998 | D | 0.693 | prob.neutral | N | 0.510263547 | None | None | N |
| D/W | 0.9955 | likely_pathogenic | 0.995 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/Y | 0.8539 | likely_pathogenic | 0.8511 | pathogenic | -0.245 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | D | 0.52963525 | 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.