Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32608 | 98047;98048;98049 | chr2:178540344;178540343;178540342 | chr2:179405071;179405070;179405069 |
| N2AB | 30967 | 93124;93125;93126 | chr2:178540344;178540343;178540342 | chr2:179405071;179405070;179405069 |
| N2A | 30040 | 90343;90344;90345 | chr2:178540344;178540343;178540342 | chr2:179405071;179405070;179405069 |
| N2B | 23543 | 70852;70853;70854 | chr2:178540344;178540343;178540342 | chr2:179405071;179405070;179405069 |
| Novex-1 | 23668 | 71227;71228;71229 | chr2:178540344;178540343;178540342 | chr2:179405071;179405070;179405069 |
| Novex-2 | 23735 | 71428;71429;71430 | chr2:178540344;178540343;178540342 | chr2:179405071;179405070;179405069 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs757187219  |
-0.641 | 0.998 | N | 0.504 | 0.321 | 0.268211541103 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.55E-05 | None | 0 | 0 | 0 |
| R/K | rs757187219 |
-0.641 | 0.998 | N | 0.504 | 0.321 | 0.268211541103 | gnomAD-4.0.0 | 1.3691E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.32029E-05 | 0 |
| R/T | rs757187219 |
None | 0.994 | N | 0.673 | 0.357 | None | gnomAD-4.0.0 | 6.8455E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87371E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5717 | likely_pathogenic | 0.5677 | pathogenic | -0.84 | Destabilizing | 0.992 | D | 0.614 | neutral | None | None | None | None | N |
| R/C | 0.1853 | likely_benign | 0.2027 | benign | -0.845 | Destabilizing | 0.46 | N | 0.482 | neutral | None | None | None | None | N |
| R/D | 0.8678 | likely_pathogenic | 0.8677 | pathogenic | -0.068 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/E | 0.4996 | ambiguous | 0.5068 | ambiguous | 0.086 | Stabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| R/F | 0.5476 | ambiguous | 0.5327 | ambiguous | -0.538 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/G | 0.5945 | likely_pathogenic | 0.594 | pathogenic | -1.182 | Destabilizing | 0.994 | D | 0.668 | neutral | N | 0.483018259 | None | None | N |
| R/H | 0.1353 | likely_benign | 0.1349 | benign | -1.441 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| R/I | 0.2638 | likely_benign | 0.2598 | benign | 0.091 | Stabilizing | 0.998 | D | 0.798 | deleterious | N | 0.472814043 | None | None | N |
| R/K | 0.1281 | likely_benign | 0.1322 | benign | -0.814 | Destabilizing | 0.998 | D | 0.504 | neutral | N | 0.432457328 | None | None | N |
| R/L | 0.3286 | likely_benign | 0.3179 | benign | 0.091 | Stabilizing | 0.992 | D | 0.659 | neutral | None | None | None | None | N |
| R/M | 0.3285 | likely_benign | 0.3254 | benign | -0.343 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| R/N | 0.7595 | likely_pathogenic | 0.7592 | pathogenic | -0.417 | Destabilizing | 1.0 | D | 0.575 | neutral | None | None | None | None | N |
| R/P | 0.982 | likely_pathogenic | 0.9794 | pathogenic | -0.199 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/Q | 0.1331 | likely_benign | 0.136 | benign | -0.489 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| R/S | 0.692 | likely_pathogenic | 0.6884 | pathogenic | -1.194 | Destabilizing | 0.994 | D | 0.673 | neutral | N | 0.508165808 | None | None | N |
| R/T | 0.3586 | ambiguous | 0.3506 | ambiguous | -0.839 | Destabilizing | 0.994 | D | 0.673 | neutral | N | 0.482654075 | None | None | N |
| R/V | 0.3111 | likely_benign | 0.3126 | benign | -0.199 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/W | 0.2573 | likely_benign | 0.2619 | benign | -0.173 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| R/Y | 0.4455 | ambiguous | 0.4458 | ambiguous | 0.102 | Stabilizing | 1.0 | D | 0.799 | deleterious | 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.