Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27873 | 83842;83843;83844 | chr2:178562515;178562514;178562513 | chr2:179427242;179427241;179427240 |
| N2AB | 26232 | 78919;78920;78921 | chr2:178562515;178562514;178562513 | chr2:179427242;179427241;179427240 |
| N2A | 25305 | 76138;76139;76140 | chr2:178562515;178562514;178562513 | chr2:179427242;179427241;179427240 |
| N2B | 18808 | 56647;56648;56649 | chr2:178562515;178562514;178562513 | chr2:179427242;179427241;179427240 |
| Novex-1 | 18933 | 57022;57023;57024 | chr2:178562515;178562514;178562513 | chr2:179427242;179427241;179427240 |
| Novex-2 | 19000 | 57223;57224;57225 | chr2:178562515;178562514;178562513 | chr2:179427242;179427241;179427240 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs200775919  |
-0.771 | 0.625 | N | 0.365 | 0.182 | None | gnomAD-2.1.1 | 2.34204E-04 | None | None | None | None | N | None | 0 | 0 | None | 4.39281E-03 | 0 | None | 0 | None | 0 | 1.33381E-04 | 4.26136E-04 |
| V/A | rs200775919 |
-0.771 | 0.625 | N | 0.365 | 0.182 | None | gnomAD-3.1.2 | 1.70945E-04 | None | None | None | None | N | None | 0 | 2.62123E-04 | 0 | 4.89631E-03 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| V/A | rs200775919 |
-0.771 | 0.625 | N | 0.365 | 0.182 | None | gnomAD-4.0.0 | 1.49534E-04 | None | None | None | None | N | None | 0 | 6.70107E-05 | None | 5.52355E-03 | 0 | None | 0 | 3.29381E-04 | 3.56148E-05 | 0 | 4.80846E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1381 | likely_benign | 0.1329 | benign | -1.002 | Destabilizing | 0.625 | D | 0.365 | neutral | N | 0.495007296 | None | None | N |
| V/C | 0.7503 | likely_pathogenic | 0.7409 | pathogenic | -0.765 | Destabilizing | 0.998 | D | 0.404 | neutral | None | None | None | None | N |
| V/D | 0.4007 | ambiguous | 0.3877 | ambiguous | -0.557 | Destabilizing | 0.669 | D | 0.463 | neutral | N | 0.467628694 | None | None | N |
| V/E | 0.2975 | likely_benign | 0.2916 | benign | -0.628 | Destabilizing | 0.067 | N | 0.311 | neutral | None | None | None | None | N |
| V/F | 0.2173 | likely_benign | 0.2293 | benign | -0.923 | Destabilizing | 0.934 | D | 0.453 | neutral | N | 0.469749396 | None | None | N |
| V/G | 0.2327 | likely_benign | 0.2315 | benign | -1.217 | Destabilizing | 0.891 | D | 0.449 | neutral | N | 0.507725877 | None | None | N |
| V/H | 0.5949 | likely_pathogenic | 0.591 | pathogenic | -0.623 | Destabilizing | 0.998 | D | 0.435 | neutral | None | None | None | None | N |
| V/I | 0.0806 | likely_benign | 0.0799 | benign | -0.554 | Destabilizing | 0.051 | N | 0.156 | neutral | N | 0.467455336 | None | None | N |
| V/K | 0.434 | ambiguous | 0.423 | ambiguous | -0.778 | Destabilizing | 0.728 | D | 0.412 | neutral | None | None | None | None | N |
| V/L | 0.1708 | likely_benign | 0.1631 | benign | -0.554 | Destabilizing | 0.005 | N | 0.081 | neutral | N | 0.462510876 | None | None | N |
| V/M | 0.1251 | likely_benign | 0.1285 | benign | -0.457 | Destabilizing | 0.949 | D | 0.425 | neutral | None | None | None | None | N |
| V/N | 0.3179 | likely_benign | 0.3101 | benign | -0.542 | Destabilizing | 0.974 | D | 0.47 | neutral | None | None | None | None | N |
| V/P | 0.8761 | likely_pathogenic | 0.8666 | pathogenic | -0.667 | Destabilizing | 0.991 | D | 0.463 | neutral | None | None | None | None | N |
| V/Q | 0.3343 | likely_benign | 0.3331 | benign | -0.779 | Destabilizing | 0.949 | D | 0.443 | neutral | None | None | None | None | N |
| V/R | 0.377 | ambiguous | 0.381 | ambiguous | -0.191 | Destabilizing | 0.037 | N | 0.373 | neutral | None | None | None | None | N |
| V/S | 0.1821 | likely_benign | 0.1816 | benign | -1.014 | Destabilizing | 0.842 | D | 0.453 | neutral | None | None | None | None | N |
| V/T | 0.109 | likely_benign | 0.1048 | benign | -0.979 | Destabilizing | 0.915 | D | 0.291 | neutral | None | None | None | None | N |
| V/W | 0.8063 | likely_pathogenic | 0.8239 | pathogenic | -0.998 | Destabilizing | 0.998 | D | 0.497 | neutral | None | None | None | None | N |
| V/Y | 0.6305 | likely_pathogenic | 0.6302 | pathogenic | -0.722 | Destabilizing | 0.991 | D | 0.443 | 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.