Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14413 | 43462;43463;43464 | chr2:178632769;178632768;178632767 | chr2:179497496;179497495;179497494 |
| N2AB | 12772 | 38539;38540;38541 | chr2:178632769;178632768;178632767 | chr2:179497496;179497495;179497494 |
| N2A | 11845 | 35758;35759;35760 | chr2:178632769;178632768;178632767 | chr2:179497496;179497495;179497494 |
| N2B | 5348 | 16267;16268;16269 | chr2:178632769;178632768;178632767 | chr2:179497496;179497495;179497494 |
| Novex-1 | 5473 | 16642;16643;16644 | chr2:178632769;178632768;178632767 | chr2:179497496;179497495;179497494 |
| Novex-2 | 5540 | 16843;16844;16845 | chr2:178632769;178632768;178632767 | chr2:179497496;179497495;179497494 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs548964329  |
-0.299 | 1.0 | D | 0.804 | 0.402 | 0.733644550584 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94099E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs548964329 |
-0.299 | 1.0 | D | 0.804 | 0.402 | 0.733644550584 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| P/L | rs548964329 |
-0.299 | 1.0 | D | 0.804 | 0.402 | 0.733644550584 | gnomAD-4.0.0 | 6.57013E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.94553E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs2059959828 |
None | 1.0 | N | 0.823 | 0.372 | 0.451310735921 | gnomAD-4.0.0 | 1.59319E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77701E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2026 | likely_benign | 0.1919 | benign | -0.951 | Destabilizing | 1.0 | D | 0.764 | deleterious | D | 0.556594979 | None | None | N |
| P/C | 0.8802 | likely_pathogenic | 0.8538 | pathogenic | -0.658 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| P/D | 0.8311 | likely_pathogenic | 0.8268 | pathogenic | -0.224 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| P/E | 0.6118 | likely_pathogenic | 0.5919 | pathogenic | -0.279 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/F | 0.8814 | likely_pathogenic | 0.8665 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| P/G | 0.6382 | likely_pathogenic | 0.6244 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| P/H | 0.4798 | ambiguous | 0.4603 | ambiguous | -0.695 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.540898263 | None | None | N |
| P/I | 0.7847 | likely_pathogenic | 0.7704 | pathogenic | -0.444 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| P/K | 0.6044 | likely_pathogenic | 0.6217 | pathogenic | -0.59 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| P/L | 0.3543 | ambiguous | 0.3276 | benign | -0.444 | Destabilizing | 1.0 | D | 0.804 | deleterious | D | 0.547832486 | None | None | N |
| P/M | 0.7436 | likely_pathogenic | 0.7178 | pathogenic | -0.366 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| P/N | 0.7395 | likely_pathogenic | 0.7319 | pathogenic | -0.327 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/Q | 0.4029 | ambiguous | 0.3786 | ambiguous | -0.521 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| P/R | 0.4022 | ambiguous | 0.3823 | ambiguous | -0.127 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.51007718 | None | None | N |
| P/S | 0.3089 | likely_benign | 0.3001 | benign | -0.861 | Destabilizing | 1.0 | D | 0.823 | deleterious | N | 0.510265871 | None | None | N |
| P/T | 0.3389 | likely_benign | 0.3333 | benign | -0.804 | Destabilizing | 1.0 | D | 0.821 | deleterious | D | 0.557744417 | None | None | N |
| P/V | 0.6262 | likely_pathogenic | 0.6007 | pathogenic | -0.576 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| P/W | 0.9419 | likely_pathogenic | 0.9243 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| P/Y | 0.8269 | likely_pathogenic | 0.8125 | pathogenic | -0.662 | Destabilizing | 1.0 | D | 0.735 | 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.