Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19526 | 58801;58802;58803 | chr2:178593724;178593723;178593722 | chr2:179458451;179458450;179458449 |
| N2AB | 17885 | 53878;53879;53880 | chr2:178593724;178593723;178593722 | chr2:179458451;179458450;179458449 |
| N2A | 16958 | 51097;51098;51099 | chr2:178593724;178593723;178593722 | chr2:179458451;179458450;179458449 |
| N2B | 10461 | 31606;31607;31608 | chr2:178593724;178593723;178593722 | chr2:179458451;179458450;179458449 |
| Novex-1 | 10586 | 31981;31982;31983 | chr2:178593724;178593723;178593722 | chr2:179458451;179458450;179458449 |
| Novex-2 | 10653 | 32182;32183;32184 | chr2:178593724;178593723;178593722 | chr2:179458451;179458450;179458449 |
| 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/F | rs377682563  |
-0.759 | 0.144 | N | 0.283 | 0.098 | 0.273503213844 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs377682563 |
-0.759 | 0.144 | N | 0.283 | 0.098 | 0.273503213844 | gnomAD-4.0.0 | 6.84375E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.52666E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs377682563 |
-0.189 | 0.001 | N | 0.13 | 0.037 | None | gnomAD-2.1.1 | 1.43085E-04 | None | None | None | None | I | None | 1.65344E-04 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.58483E-04 | 1.40528E-04 |
| V/I | rs377682563 |
-0.189 | 0.001 | N | 0.13 | 0.037 | None | gnomAD-3.1.2 | 1.90779E-04 | None | None | None | None | I | None | 7.25E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 3.53045E-04 | 0 | 4.78927E-04 |
| V/I | rs377682563 |
-0.189 | 0.001 | N | 0.13 | 0.037 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| V/I | rs377682563 |
-0.189 | 0.001 | N | 0.13 | 0.037 | None | gnomAD-4.0.0 | 3.30376E-04 | None | None | None | None | I | None | 8.00149E-05 | 3.33589E-05 | None | 0 | 0 | None | 0 | 1.65125E-04 | 4.22179E-04 | 7.68707E-05 | 3.04185E-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 | 0.1917 | likely_benign | 0.1277 | benign | -0.699 | Destabilizing | 0.052 | N | 0.25 | neutral | N | 0.466223185 | None | None | I |
| V/C | 0.6174 | likely_pathogenic | 0.4588 | ambiguous | -0.391 | Destabilizing | 0.935 | D | 0.239 | neutral | None | None | None | None | I |
| V/D | 0.326 | likely_benign | 0.2176 | benign | -0.686 | Destabilizing | 0.484 | N | 0.333 | neutral | N | 0.451272375 | None | None | I |
| V/E | 0.3238 | likely_benign | 0.2155 | benign | -0.771 | Destabilizing | 0.555 | D | 0.313 | neutral | None | None | None | None | I |
| V/F | 0.1572 | likely_benign | 0.1115 | benign | -0.797 | Destabilizing | 0.144 | N | 0.283 | neutral | N | 0.520135027 | None | None | I |
| V/G | 0.2076 | likely_benign | 0.1487 | benign | -0.881 | Destabilizing | 0.484 | N | 0.333 | neutral | N | 0.451619091 | None | None | I |
| V/H | 0.5046 | ambiguous | 0.3492 | ambiguous | -0.476 | Destabilizing | 0.935 | D | 0.305 | neutral | None | None | None | None | I |
| V/I | 0.0711 | likely_benign | 0.0635 | benign | -0.344 | Destabilizing | 0.001 | N | 0.13 | neutral | N | 0.473093229 | None | None | I |
| V/K | 0.3777 | ambiguous | 0.2465 | benign | -0.615 | Destabilizing | 0.555 | D | 0.308 | neutral | None | None | None | None | I |
| V/L | 0.1484 | likely_benign | 0.095 | benign | -0.344 | Destabilizing | None | N | 0.084 | neutral | N | 0.441076811 | None | None | I |
| V/M | 0.133 | likely_benign | 0.0928 | benign | -0.331 | Destabilizing | 0.38 | N | 0.261 | neutral | None | None | None | None | I |
| V/N | 0.2105 | likely_benign | 0.1348 | benign | -0.231 | Destabilizing | 0.791 | D | 0.313 | neutral | None | None | None | None | I |
| V/P | 0.6438 | likely_pathogenic | 0.5277 | ambiguous | -0.428 | Destabilizing | 0.791 | D | 0.313 | neutral | None | None | None | None | I |
| V/Q | 0.3229 | likely_benign | 0.222 | benign | -0.475 | Destabilizing | 0.791 | D | 0.291 | neutral | None | None | None | None | I |
| V/R | 0.3294 | likely_benign | 0.2124 | benign | -0.081 | Destabilizing | 0.555 | D | 0.325 | neutral | None | None | None | None | I |
| V/S | 0.1895 | likely_benign | 0.1278 | benign | -0.556 | Destabilizing | 0.262 | N | 0.297 | neutral | None | None | None | None | I |
| V/T | 0.1795 | likely_benign | 0.1214 | benign | -0.547 | Destabilizing | 0.149 | N | 0.206 | neutral | None | None | None | None | I |
| V/W | 0.7087 | likely_pathogenic | 0.5594 | ambiguous | -0.918 | Destabilizing | 0.935 | D | 0.337 | neutral | None | None | None | None | I |
| V/Y | 0.4266 | ambiguous | 0.2953 | benign | -0.625 | Destabilizing | 0.555 | D | 0.265 | neutral | None | None | None | None | I |
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.