Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2282 | 7069;7070;7071 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
| N2AB | 2282 | 7069;7070;7071 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
| N2A | 2282 | 7069;7070;7071 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
| N2B | 2236 | 6931;6932;6933 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
| Novex-1 | 2236 | 6931;6932;6933 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
| Novex-2 | 2236 | 6931;6932;6933 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
| Novex-3 | 2282 | 7069;7070;7071 | chr2:178774420;178774419;178774418 | chr2:179639147;179639146;179639145 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | None | None | None | N | 0.157 | 0.057 | 0.101711395817 | gnomAD-4.0.0 | 6.84216E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15937E-05 | 0 |
| Y/H | rs727503691  |
None | 0.484 | N | 0.33 | 0.148 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs727503691 |
None | 0.484 | N | 0.33 | 0.148 | None | gnomAD-4.0.0 | 2.47906E-06 | None | None | None | None | N | None | 4.00374E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47629E-07 | 0 | 0 |
| Y/S | rs754307416 |
-1.211 | 0.211 | N | 0.295 | 0.146 | 0.239305524855 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/S | rs754307416 |
-1.211 | 0.211 | N | 0.295 | 0.146 | 0.239305524855 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.77555E-04 |
| Y/S | rs754307416 |
-1.211 | 0.211 | N | 0.295 | 0.146 | 0.239305524855 | gnomAD-4.0.0 | 4.33773E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.6442E-04 | 1.69499E-06 | 2.19578E-05 | 3.20082E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4816 | ambiguous | 0.3349 | benign | -0.871 | Destabilizing | 0.149 | N | 0.337 | neutral | None | None | None | None | N |
| Y/C | 0.1801 | likely_benign | 0.1327 | benign | -0.16 | Destabilizing | 0.915 | D | 0.297 | neutral | N | 0.447719041 | None | None | N |
| Y/D | 0.5482 | ambiguous | 0.4072 | ambiguous | 0.983 | Stabilizing | 0.741 | D | 0.317 | neutral | N | 0.348347129 | None | None | N |
| Y/E | 0.7676 | likely_pathogenic | 0.6443 | pathogenic | 0.985 | Stabilizing | 0.555 | D | 0.295 | neutral | None | None | None | None | N |
| Y/F | 0.0509 | likely_benign | 0.0508 | benign | -0.377 | Destabilizing | None | N | 0.157 | neutral | N | 0.433816223 | None | None | N |
| Y/G | 0.5407 | ambiguous | 0.4272 | ambiguous | -1.073 | Destabilizing | 0.262 | N | 0.327 | neutral | None | None | None | None | N |
| Y/H | 0.2759 | likely_benign | 0.2101 | benign | 0.131 | Stabilizing | 0.484 | N | 0.33 | neutral | N | 0.424646796 | None | None | N |
| Y/I | 0.4425 | ambiguous | 0.3097 | benign | -0.348 | Destabilizing | 0.081 | N | 0.317 | neutral | None | None | None | None | N |
| Y/K | 0.7928 | likely_pathogenic | 0.6766 | pathogenic | 0.002 | Stabilizing | 0.555 | D | 0.293 | neutral | None | None | None | None | N |
| Y/L | 0.5724 | likely_pathogenic | 0.3868 | ambiguous | -0.348 | Destabilizing | None | N | 0.168 | neutral | None | None | None | None | N |
| Y/M | 0.582 | likely_pathogenic | 0.4331 | ambiguous | -0.242 | Destabilizing | 0.38 | N | 0.299 | neutral | None | None | None | None | N |
| Y/N | 0.2911 | likely_benign | 0.2123 | benign | -0.248 | Destabilizing | 0.741 | D | 0.307 | neutral | N | 0.435713314 | None | None | N |
| Y/P | 0.9743 | likely_pathogenic | 0.953 | pathogenic | -0.504 | Destabilizing | 0.791 | D | 0.315 | neutral | None | None | None | None | N |
| Y/Q | 0.6157 | likely_pathogenic | 0.4799 | ambiguous | -0.158 | Destabilizing | 0.791 | D | 0.3 | neutral | None | None | None | None | N |
| Y/R | 0.6431 | likely_pathogenic | 0.5226 | ambiguous | 0.264 | Stabilizing | 0.555 | D | 0.303 | neutral | None | None | None | None | N |
| Y/S | 0.2283 | likely_benign | 0.1614 | benign | -0.753 | Destabilizing | 0.211 | N | 0.295 | neutral | N | 0.420530684 | None | None | N |
| Y/T | 0.4661 | ambiguous | 0.3274 | benign | -0.658 | Destabilizing | 0.149 | N | 0.308 | neutral | None | None | None | None | N |
| Y/V | 0.3614 | ambiguous | 0.2479 | benign | -0.504 | Destabilizing | 0.035 | N | 0.326 | neutral | None | None | None | None | N |
| Y/W | 0.4396 | ambiguous | 0.3978 | ambiguous | -0.421 | Destabilizing | 0.555 | D | 0.339 | 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.