Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16319 | 49180;49181;49182 | chr2:178614559;178614558;178614557 | chr2:179479286;179479285;179479284 |
| N2AB | 14678 | 44257;44258;44259 | chr2:178614559;178614558;178614557 | chr2:179479286;179479285;179479284 |
| N2A | 13751 | 41476;41477;41478 | chr2:178614559;178614558;178614557 | chr2:179479286;179479285;179479284 |
| N2B | 7254 | 21985;21986;21987 | chr2:178614559;178614558;178614557 | chr2:179479286;179479285;179479284 |
| Novex-1 | 7379 | 22360;22361;22362 | chr2:178614559;178614558;178614557 | chr2:179479286;179479285;179479284 |
| Novex-2 | 7446 | 22561;22562;22563 | chr2:178614559;178614558;178614557 | chr2:179479286;179479285;179479284 |
| 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 | rs374837771  |
-1.389 | None | N | 0.109 | 0.135 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| V/A | rs374837771 |
-1.389 | None | N | 0.109 | 0.135 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/A | rs374837771 |
-1.389 | None | N | 0.109 | 0.135 | None | gnomAD-4.0.0 | 1.9227E-05 | None | None | None | None | N | None | 2.67437E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.45936E-05 | 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 | 0.0698 | likely_benign | 0.07 | benign | -1.29 | Destabilizing | None | N | 0.109 | neutral | N | 0.379595691 | None | None | N |
| V/C | 0.4259 | ambiguous | 0.4406 | ambiguous | -1.251 | Destabilizing | 0.356 | N | 0.425 | neutral | None | None | None | None | N |
| V/D | 0.2165 | likely_benign | 0.1865 | benign | -1.213 | Destabilizing | 0.029 | N | 0.479 | neutral | N | 0.426838213 | None | None | N |
| V/E | 0.1697 | likely_benign | 0.1564 | benign | -1.253 | Destabilizing | None | N | 0.199 | neutral | None | None | None | None | N |
| V/F | 0.125 | likely_benign | 0.1279 | benign | -1.245 | Destabilizing | 0.029 | N | 0.497 | neutral | N | 0.487852958 | None | None | N |
| V/G | 0.1163 | likely_benign | 0.1201 | benign | -1.533 | Destabilizing | 0.012 | N | 0.421 | neutral | N | 0.480224975 | None | None | N |
| V/H | 0.2697 | likely_benign | 0.2587 | benign | -0.975 | Destabilizing | 0.356 | N | 0.473 | neutral | None | None | None | None | N |
| V/I | 0.0648 | likely_benign | 0.0653 | benign | -0.745 | Destabilizing | 0.012 | N | 0.281 | neutral | N | 0.474767101 | None | None | N |
| V/K | 0.1577 | likely_benign | 0.1432 | benign | -0.931 | Destabilizing | 0.016 | N | 0.431 | neutral | None | None | None | None | N |
| V/L | 0.0933 | likely_benign | 0.0973 | benign | -0.745 | Destabilizing | None | N | 0.119 | neutral | N | 0.441473233 | None | None | N |
| V/M | 0.0751 | likely_benign | 0.0834 | benign | -0.686 | Destabilizing | 0.001 | N | 0.234 | neutral | None | None | None | None | N |
| V/N | 0.1194 | likely_benign | 0.1042 | benign | -0.784 | Destabilizing | 0.072 | N | 0.529 | neutral | None | None | None | None | N |
| V/P | 0.3334 | likely_benign | 0.3324 | benign | -0.893 | Destabilizing | 0.136 | N | 0.513 | neutral | None | None | None | None | N |
| V/Q | 0.1595 | likely_benign | 0.1529 | benign | -1.056 | Destabilizing | 0.038 | N | 0.505 | neutral | None | None | None | None | N |
| V/R | 0.1588 | likely_benign | 0.1523 | benign | -0.404 | Destabilizing | 0.072 | N | 0.534 | neutral | None | None | None | None | N |
| V/S | 0.0827 | likely_benign | 0.0778 | benign | -1.3 | Destabilizing | 0.016 | N | 0.36 | neutral | None | None | None | None | N |
| V/T | 0.0587 | likely_benign | 0.0585 | benign | -1.236 | Destabilizing | None | N | 0.108 | neutral | None | None | None | None | N |
| V/W | 0.5739 | likely_pathogenic | 0.6099 | pathogenic | -1.309 | Destabilizing | 0.864 | D | 0.462 | neutral | None | None | None | None | N |
| V/Y | 0.3303 | likely_benign | 0.3342 | benign | -0.997 | Destabilizing | 0.356 | N | 0.477 | 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.