Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20331 | 61216;61217;61218 | chr2:178590734;178590733;178590732 | chr2:179455461;179455460;179455459 |
| N2AB | 18690 | 56293;56294;56295 | chr2:178590734;178590733;178590732 | chr2:179455461;179455460;179455459 |
| N2A | 17763 | 53512;53513;53514 | chr2:178590734;178590733;178590732 | chr2:179455461;179455460;179455459 |
| N2B | 11266 | 34021;34022;34023 | chr2:178590734;178590733;178590732 | chr2:179455461;179455460;179455459 |
| Novex-1 | 11391 | 34396;34397;34398 | chr2:178590734;178590733;178590732 | chr2:179455461;179455460;179455459 |
| Novex-2 | 11458 | 34597;34598;34599 | chr2:178590734;178590733;178590732 | chr2:179455461;179455460;179455459 |
| 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/G | rs1226541281  |
-1.096 | None | N | 0.366 | 0.147 | 0.243398259712 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.59E-05 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs1226541281 |
-1.096 | None | N | 0.366 | 0.147 | 0.243398259712 | gnomAD-4.0.0 | 1.5952E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77901E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7307 | likely_pathogenic | 0.7583 | pathogenic | -0.574 | Destabilizing | 0.035 | N | 0.519 | neutral | None | None | None | None | N |
| R/C | 0.2637 | likely_benign | 0.2953 | benign | -0.534 | Destabilizing | 0.824 | D | 0.6 | neutral | None | None | None | None | N |
| R/D | 0.9173 | likely_pathogenic | 0.9308 | pathogenic | 0.031 | Stabilizing | 0.38 | N | 0.593 | neutral | None | None | None | None | N |
| R/E | 0.6807 | likely_pathogenic | 0.7205 | pathogenic | 0.143 | Stabilizing | 0.149 | N | 0.547 | neutral | None | None | None | None | N |
| R/F | 0.7999 | likely_pathogenic | 0.8234 | pathogenic | -0.549 | Destabilizing | 0.555 | D | 0.589 | neutral | None | None | None | None | N |
| R/G | 0.6987 | likely_pathogenic | 0.7293 | pathogenic | -0.856 | Destabilizing | None | N | 0.366 | neutral | N | 0.468988928 | None | None | N |
| R/H | 0.1503 | likely_benign | 0.1838 | benign | -1.301 | Destabilizing | 0.791 | D | 0.554 | neutral | None | None | None | None | N |
| R/I | 0.4922 | ambiguous | 0.5091 | ambiguous | 0.168 | Stabilizing | 0.188 | N | 0.603 | neutral | N | 0.497450169 | None | None | N |
| R/K | 0.15 | likely_benign | 0.185 | benign | -0.519 | Destabilizing | 0.002 | N | 0.225 | neutral | N | 0.396901959 | None | None | N |
| R/L | 0.4445 | ambiguous | 0.4773 | ambiguous | 0.168 | Stabilizing | 0.081 | N | 0.547 | neutral | None | None | None | None | N |
| R/M | 0.5104 | ambiguous | 0.5399 | ambiguous | -0.19 | Destabilizing | 0.824 | D | 0.566 | neutral | None | None | None | None | N |
| R/N | 0.8414 | likely_pathogenic | 0.8677 | pathogenic | -0.071 | Destabilizing | 0.149 | N | 0.551 | neutral | None | None | None | None | N |
| R/P | 0.7943 | likely_pathogenic | 0.7917 | pathogenic | -0.058 | Destabilizing | 0.555 | D | 0.605 | neutral | None | None | None | None | N |
| R/Q | 0.1714 | likely_benign | 0.1952 | benign | -0.224 | Destabilizing | 0.38 | N | 0.579 | neutral | None | None | None | None | N |
| R/S | 0.7989 | likely_pathogenic | 0.8219 | pathogenic | -0.751 | Destabilizing | 0.062 | N | 0.549 | neutral | N | 0.486675815 | None | None | N |
| R/T | 0.4812 | ambiguous | 0.4795 | ambiguous | -0.462 | Destabilizing | None | N | 0.365 | neutral | N | 0.418618452 | None | None | N |
| R/V | 0.5608 | ambiguous | 0.5966 | pathogenic | -0.058 | Destabilizing | 0.081 | N | 0.591 | neutral | None | None | None | None | N |
| R/W | 0.2899 | likely_benign | 0.3051 | benign | -0.318 | Destabilizing | 0.935 | D | 0.647 | neutral | None | None | None | None | N |
| R/Y | 0.6186 | likely_pathogenic | 0.6619 | pathogenic | 0.013 | Stabilizing | 0.555 | D | 0.589 | 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.