Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27510 | 82753;82754;82755 | chr2:178563604;178563603;178563602 | chr2:179428331;179428330;179428329 |
| N2AB | 25869 | 77830;77831;77832 | chr2:178563604;178563603;178563602 | chr2:179428331;179428330;179428329 |
| N2A | 24942 | 75049;75050;75051 | chr2:178563604;178563603;178563602 | chr2:179428331;179428330;179428329 |
| N2B | 18445 | 55558;55559;55560 | chr2:178563604;178563603;178563602 | chr2:179428331;179428330;179428329 |
| Novex-1 | 18570 | 55933;55934;55935 | chr2:178563604;178563603;178563602 | chr2:179428331;179428330;179428329 |
| Novex-2 | 18637 | 56134;56135;56136 | chr2:178563604;178563603;178563602 | chr2:179428331;179428330;179428329 |
| 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 | rs747295333  |
-0.963 | 0.958 | N | 0.691 | 0.433 | 0.384919354899 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs747295333 |
-0.963 | 0.958 | N | 0.691 | 0.433 | 0.384919354899 | gnomAD-4.0.0 | 1.59125E-06 | None | None | None | None | N | None | 0 | 2.28634E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | None | None | 0.988 | N | 0.644 | 0.383 | 0.457013227636 | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85838E-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 | 0.839 | likely_pathogenic | 0.8087 | pathogenic | -0.464 | Destabilizing | 0.988 | D | 0.681 | prob.neutral | N | 0.466164544 | None | None | N |
| D/C | 0.9309 | likely_pathogenic | 0.9198 | pathogenic | -0.332 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| D/E | 0.6007 | likely_pathogenic | 0.5607 | ambiguous | -0.78 | Destabilizing | 0.067 | N | 0.263 | neutral | N | 0.44040202 | None | None | N |
| D/F | 0.959 | likely_pathogenic | 0.9527 | pathogenic | 0.054 | Stabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| D/G | 0.7922 | likely_pathogenic | 0.7664 | pathogenic | -0.901 | Destabilizing | 0.958 | D | 0.691 | prob.neutral | N | 0.481497322 | None | None | N |
| D/H | 0.852 | likely_pathogenic | 0.8336 | pathogenic | -0.476 | Destabilizing | 0.998 | D | 0.77 | deleterious | N | 0.504374517 | None | None | N |
| D/I | 0.9445 | likely_pathogenic | 0.929 | pathogenic | 0.722 | Stabilizing | 0.995 | D | 0.821 | deleterious | None | None | None | None | N |
| D/K | 0.9539 | likely_pathogenic | 0.942 | pathogenic | -1.012 | Destabilizing | 0.982 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/L | 0.9001 | likely_pathogenic | 0.8848 | pathogenic | 0.722 | Stabilizing | 0.991 | D | 0.817 | deleterious | None | None | None | None | N |
| D/M | 0.9695 | likely_pathogenic | 0.9614 | pathogenic | 1.316 | Stabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/N | 0.5132 | ambiguous | 0.4682 | ambiguous | -1.415 | Destabilizing | 0.988 | D | 0.644 | neutral | N | 0.479495859 | None | None | N |
| D/P | 0.9868 | likely_pathogenic | 0.9845 | pathogenic | 0.352 | Stabilizing | 0.995 | D | 0.817 | deleterious | None | None | None | None | N |
| D/Q | 0.8878 | likely_pathogenic | 0.8656 | pathogenic | -1.119 | Destabilizing | 0.982 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/R | 0.9348 | likely_pathogenic | 0.9248 | pathogenic | -0.908 | Destabilizing | 0.991 | D | 0.794 | deleterious | None | None | None | None | N |
| D/S | 0.6546 | likely_pathogenic | 0.6109 | pathogenic | -1.827 | Destabilizing | 0.968 | D | 0.597 | neutral | None | None | None | None | N |
| D/T | 0.9128 | likely_pathogenic | 0.8842 | pathogenic | -1.457 | Destabilizing | 0.991 | D | 0.783 | deleterious | None | None | None | None | N |
| D/V | 0.8664 | likely_pathogenic | 0.8383 | pathogenic | 0.352 | Stabilizing | 0.994 | D | 0.819 | deleterious | N | 0.480509817 | None | None | N |
| D/W | 0.9845 | likely_pathogenic | 0.9814 | pathogenic | 0.053 | Stabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/Y | 0.7851 | likely_pathogenic | 0.7568 | pathogenic | 0.218 | Stabilizing | 0.999 | D | 0.793 | deleterious | D | 0.528101086 | 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.