Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22333 | 67222;67223;67224 | chr2:178580382;178580381;178580380 | chr2:179445109;179445108;179445107 |
| N2AB | 20692 | 62299;62300;62301 | chr2:178580382;178580381;178580380 | chr2:179445109;179445108;179445107 |
| N2A | 19765 | 59518;59519;59520 | chr2:178580382;178580381;178580380 | chr2:179445109;179445108;179445107 |
| N2B | 13268 | 40027;40028;40029 | chr2:178580382;178580381;178580380 | chr2:179445109;179445108;179445107 |
| Novex-1 | 13393 | 40402;40403;40404 | chr2:178580382;178580381;178580380 | chr2:179445109;179445108;179445107 |
| Novex-2 | 13460 | 40603;40604;40605 | chr2:178580382;178580381;178580380 | chr2:179445109;179445108;179445107 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs2154176318  |
None | 0.379 | N | 0.468 | 0.271 | 0.385417323374 | gnomAD-4.0.0 | 1.59245E-06 | None | None | None | None | N | None | 0 | 2.28676E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs753147042 |
-1.398 | 0.001 | N | 0.123 | 0.047 | 0.307332253619 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs753147042 |
-1.398 | 0.001 | N | 0.123 | 0.047 | 0.307332253619 | gnomAD-4.0.0 | 1.59244E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43332E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3849 | ambiguous | 0.3772 | ambiguous | -2.363 | Highly Destabilizing | 0.25 | N | 0.494 | neutral | None | None | None | None | N |
| I/C | 0.5829 | likely_pathogenic | 0.5927 | pathogenic | -1.676 | Destabilizing | 0.977 | D | 0.506 | neutral | None | None | None | None | N |
| I/D | 0.7513 | likely_pathogenic | 0.7611 | pathogenic | -2.059 | Highly Destabilizing | 0.85 | D | 0.604 | neutral | None | None | None | None | N |
| I/E | 0.5768 | likely_pathogenic | 0.6088 | pathogenic | -1.906 | Destabilizing | 0.617 | D | 0.606 | neutral | None | None | None | None | N |
| I/F | 0.1915 | likely_benign | 0.1886 | benign | -1.398 | Destabilizing | 0.81 | D | 0.462 | neutral | N | 0.498767172 | None | None | N |
| I/G | 0.6869 | likely_pathogenic | 0.6842 | pathogenic | -2.854 | Highly Destabilizing | 0.447 | N | 0.577 | neutral | None | None | None | None | N |
| I/H | 0.3467 | ambiguous | 0.3789 | ambiguous | -2.118 | Highly Destabilizing | 0.992 | D | 0.614 | neutral | None | None | None | None | N |
| I/K | 0.292 | likely_benign | 0.3339 | benign | -1.738 | Destabilizing | 0.85 | D | 0.606 | neutral | None | None | None | None | N |
| I/L | 0.1381 | likely_benign | 0.1431 | benign | -0.986 | Destabilizing | 0.099 | N | 0.356 | neutral | N | 0.505885146 | None | None | N |
| I/M | 0.1244 | likely_benign | 0.1246 | benign | -0.911 | Destabilizing | 0.81 | D | 0.477 | neutral | N | 0.492841278 | None | None | N |
| I/N | 0.2126 | likely_benign | 0.2352 | benign | -1.828 | Destabilizing | 0.81 | D | 0.61 | neutral | N | 0.506925296 | None | None | N |
| I/P | 0.975 | likely_pathogenic | 0.9754 | pathogenic | -1.42 | Destabilizing | 0.92 | D | 0.616 | neutral | None | None | None | None | N |
| I/Q | 0.3673 | ambiguous | 0.4036 | ambiguous | -1.804 | Destabilizing | 0.85 | D | 0.629 | neutral | None | None | None | None | N |
| I/R | 0.2348 | likely_benign | 0.266 | benign | -1.328 | Destabilizing | 0.85 | D | 0.621 | neutral | None | None | None | None | N |
| I/S | 0.23 | likely_benign | 0.2421 | benign | -2.597 | Highly Destabilizing | 0.016 | N | 0.462 | neutral | N | 0.468020191 | None | None | N |
| I/T | 0.1465 | likely_benign | 0.141 | benign | -2.304 | Highly Destabilizing | 0.379 | N | 0.468 | neutral | N | 0.364967607 | None | None | N |
| I/V | 0.0759 | likely_benign | 0.069 | benign | -1.42 | Destabilizing | 0.001 | N | 0.123 | neutral | N | 0.400661835 | None | None | N |
| I/W | 0.8301 | likely_pathogenic | 0.8274 | pathogenic | -1.636 | Destabilizing | 0.992 | D | 0.687 | prob.neutral | None | None | None | None | N |
| I/Y | 0.4351 | ambiguous | 0.4856 | ambiguous | -1.391 | Destabilizing | 0.92 | D | 0.527 | neutral | 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.