Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21232 | 63919;63920;63921 | chr2:178587615;178587614;178587613 | chr2:179452342;179452341;179452340 |
| N2AB | 19591 | 58996;58997;58998 | chr2:178587615;178587614;178587613 | chr2:179452342;179452341;179452340 |
| N2A | 18664 | 56215;56216;56217 | chr2:178587615;178587614;178587613 | chr2:179452342;179452341;179452340 |
| N2B | 12167 | 36724;36725;36726 | chr2:178587615;178587614;178587613 | chr2:179452342;179452341;179452340 |
| Novex-1 | 12292 | 37099;37100;37101 | chr2:178587615;178587614;178587613 | chr2:179452342;179452341;179452340 |
| Novex-2 | 12359 | 37300;37301;37302 | chr2:178587615;178587614;178587613 | chr2:179452342;179452341;179452340 |
| 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/I | rs767582181  |
-0.28 | 0.767 | N | 0.321 | 0.185 | 0.474248596982 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| V/I | rs767582181 |
-0.28 | 0.767 | N | 0.321 | 0.185 | 0.474248596982 | gnomAD-4.0.0 | 6.84705E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99748E-07 | 0 | 0 |
| V/L | None | None | 0.981 | N | 0.438 | 0.262 | 0.593771126905 | gnomAD-4.0.0 | 6.84705E-07 | None | None | None | None | I | None | 2.9915E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 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 | 0.5715 | likely_pathogenic | 0.6232 | pathogenic | -1.699 | Destabilizing | 0.998 | D | 0.483 | neutral | N | 0.498708157 | None | None | I |
| V/C | 0.8274 | likely_pathogenic | 0.8747 | pathogenic | -1.22 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| V/D | 0.8275 | likely_pathogenic | 0.8498 | pathogenic | -1.818 | Destabilizing | 1.0 | D | 0.811 | deleterious | N | 0.504988807 | None | None | I |
| V/E | 0.6695 | likely_pathogenic | 0.7017 | pathogenic | -1.738 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| V/F | 0.4335 | ambiguous | 0.4709 | ambiguous | -1.05 | Destabilizing | 0.999 | D | 0.779 | deleterious | N | 0.489909519 | None | None | I |
| V/G | 0.6437 | likely_pathogenic | 0.7024 | pathogenic | -2.099 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | D | 0.527954907 | None | None | I |
| V/H | 0.8224 | likely_pathogenic | 0.8668 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| V/I | 0.0991 | likely_benign | 0.1053 | benign | -0.656 | Destabilizing | 0.767 | D | 0.321 | neutral | N | 0.48724711 | None | None | I |
| V/K | 0.7982 | likely_pathogenic | 0.8334 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| V/L | 0.2818 | likely_benign | 0.373 | ambiguous | -0.656 | Destabilizing | 0.981 | D | 0.438 | neutral | N | 0.496925386 | None | None | I |
| V/M | 0.2917 | likely_benign | 0.341 | ambiguous | -0.581 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | I |
| V/N | 0.6346 | likely_pathogenic | 0.6912 | pathogenic | -1.513 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | I |
| V/P | 0.9724 | likely_pathogenic | 0.9809 | pathogenic | -0.971 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| V/Q | 0.6424 | likely_pathogenic | 0.6888 | pathogenic | -1.563 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | I |
| V/R | 0.7204 | likely_pathogenic | 0.7466 | pathogenic | -1.162 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| V/S | 0.557 | ambiguous | 0.606 | pathogenic | -2.07 | Highly Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| V/T | 0.4541 | ambiguous | 0.4923 | ambiguous | -1.877 | Destabilizing | 0.998 | D | 0.575 | neutral | None | None | None | None | I |
| V/W | 0.9405 | likely_pathogenic | 0.9607 | pathogenic | -1.387 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | I |
| V/Y | 0.7793 | likely_pathogenic | 0.8198 | pathogenic | -1.074 | Destabilizing | 1.0 | D | 0.789 | deleterious | 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.