Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33348 | 100267;100268;100269 | chr2:178537067;178537066;178537065 | chr2:179401794;179401793;179401792 |
| N2AB | 31707 | 95344;95345;95346 | chr2:178537067;178537066;178537065 | chr2:179401794;179401793;179401792 |
| N2A | 30780 | 92563;92564;92565 | chr2:178537067;178537066;178537065 | chr2:179401794;179401793;179401792 |
| N2B | 24283 | 73072;73073;73074 | chr2:178537067;178537066;178537065 | chr2:179401794;179401793;179401792 |
| Novex-1 | 24408 | 73447;73448;73449 | chr2:178537067;178537066;178537065 | chr2:179401794;179401793;179401792 |
| Novex-2 | 24475 | 73648;73649;73650 | chr2:178537067;178537066;178537065 | chr2:179401794;179401793;179401792 |
| 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 | rs957996377  |
None | 0.139 | N | 0.128 | 0.172 | 0.417460480802 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs957996377 |
None | 0.139 | N | 0.128 | 0.172 | 0.417460480802 | gnomAD-4.0.0 | 3.84645E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.1836E-06 | 0 | 0 |
| V/M | rs757184326 |
-0.311 | 0.975 | N | 0.354 | 0.221 | 0.457741393631 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.31527E-04 | None | 0 | 0 | 0 |
| V/M | rs757184326 |
-0.311 | 0.975 | N | 0.354 | 0.221 | 0.457741393631 | gnomAD-4.0.0 | 9.58358E-06 | None | None | None | None | I | None | 0 | 2.24165E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.50949E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1451 | likely_benign | 0.1186 | benign | -0.964 | Destabilizing | 0.139 | N | 0.128 | neutral | N | 0.415698364 | None | None | I |
| V/C | 0.6533 | likely_pathogenic | 0.6305 | pathogenic | -0.726 | Destabilizing | 0.995 | D | 0.322 | neutral | None | None | None | None | I |
| V/D | 0.3794 | ambiguous | 0.3615 | ambiguous | -0.528 | Destabilizing | 0.704 | D | 0.307 | neutral | None | None | None | None | I |
| V/E | 0.3182 | likely_benign | 0.33 | benign | -0.512 | Destabilizing | 0.642 | D | 0.289 | neutral | N | 0.386490178 | None | None | I |
| V/F | 0.2656 | likely_benign | 0.2414 | benign | -0.688 | Destabilizing | 0.981 | D | 0.364 | neutral | None | None | None | None | I |
| V/G | 0.1137 | likely_benign | 0.0825 | benign | -1.244 | Destabilizing | 0.001 | N | 0.24 | neutral | N | 0.37862563 | None | None | I |
| V/H | 0.5952 | likely_pathogenic | 0.5901 | pathogenic | -0.554 | Destabilizing | 0.981 | D | 0.331 | neutral | None | None | None | None | I |
| V/I | 0.1209 | likely_benign | 0.1104 | benign | -0.304 | Destabilizing | 0.665 | D | 0.245 | neutral | None | None | None | None | I |
| V/K | 0.4181 | ambiguous | 0.4278 | ambiguous | -0.686 | Destabilizing | 0.704 | D | 0.29 | neutral | None | None | None | None | I |
| V/L | 0.2742 | likely_benign | 0.2369 | benign | -0.304 | Destabilizing | 0.6 | D | 0.249 | neutral | N | 0.454526111 | None | None | I |
| V/M | 0.2001 | likely_benign | 0.1678 | benign | -0.455 | Destabilizing | 0.975 | D | 0.354 | neutral | N | 0.466340615 | None | None | I |
| V/N | 0.2205 | likely_benign | 0.1905 | benign | -0.664 | Destabilizing | 0.704 | D | 0.314 | neutral | None | None | None | None | I |
| V/P | 0.7759 | likely_pathogenic | 0.7291 | pathogenic | -0.49 | Destabilizing | 0.828 | D | 0.33 | neutral | None | None | None | None | I |
| V/Q | 0.3051 | likely_benign | 0.3112 | benign | -0.744 | Destabilizing | 0.944 | D | 0.363 | neutral | None | None | None | None | I |
| V/R | 0.3642 | ambiguous | 0.3878 | ambiguous | -0.267 | Destabilizing | 0.944 | D | 0.385 | neutral | None | None | None | None | I |
| V/S | 0.1373 | likely_benign | 0.1163 | benign | -1.163 | Destabilizing | 0.037 | N | 0.224 | neutral | None | None | None | None | I |
| V/T | 0.1404 | likely_benign | 0.1276 | benign | -1.022 | Destabilizing | 0.329 | N | 0.185 | neutral | None | None | None | None | I |
| V/W | 0.8797 | likely_pathogenic | 0.8725 | pathogenic | -0.858 | Destabilizing | 0.995 | D | 0.335 | neutral | None | None | None | None | I |
| V/Y | 0.6449 | likely_pathogenic | 0.6288 | pathogenic | -0.526 | Destabilizing | 0.981 | D | 0.337 | 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.