Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33661 | 101206;101207;101208 | chr2:178535634;178535633;178535632 | chr2:179400361;179400360;179400359 |
| N2AB | 32020 | 96283;96284;96285 | chr2:178535634;178535633;178535632 | chr2:179400361;179400360;179400359 |
| N2A | 31093 | 93502;93503;93504 | chr2:178535634;178535633;178535632 | chr2:179400361;179400360;179400359 |
| N2B | 24596 | 74011;74012;74013 | chr2:178535634;178535633;178535632 | chr2:179400361;179400360;179400359 |
| Novex-1 | 24721 | 74386;74387;74388 | chr2:178535634;178535633;178535632 | chr2:179400361;179400360;179400359 |
| Novex-2 | 24788 | 74587;74588;74589 | chr2:178535634;178535633;178535632 | chr2:179400361;179400360;179400359 |
| 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 | rs998389353  |
-0.544 | 1.0 | N | 0.567 | 0.356 | 0.385417323374 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs998389353 |
-0.544 | 1.0 | N | 0.567 | 0.356 | 0.385417323374 | gnomAD-4.0.0 | 2.05263E-06 | None | None | None | None | N | None | 0 | 4.47207E-05 | None | 0 | 0 | None | 0 | 0 | 8.99467E-07 | 0 | 0 |
| R/K | rs201857158 |
0.101 | 0.972 | N | 0.505 | 0.223 | 0.136095386433 | gnomAD-2.1.1 | 3.60869E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.17035E-03 | None | 0 | 0 | 5.61798E-04 |
| R/K | rs201857158 |
0.101 | 0.972 | N | 0.505 | 0.223 | 0.136095386433 | gnomAD-3.1.2 | 1.3143E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.13736E-03 | 0 |
| R/K | rs201857158 |
0.101 | 0.972 | N | 0.505 | 0.223 | 0.136095386433 | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 4.1E-03 | None |
| R/K | rs201857158 |
0.101 | 0.972 | N | 0.505 | 0.223 | 0.136095386433 | gnomAD-4.0.0 | 2.05723E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22846E-05 | None | 0 | 1.65017E-04 | 2.54281E-06 | 3.46933E-03 | 1.76056E-04 |
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 | 0.866 | likely_pathogenic | 0.6867 | pathogenic | 0.007 | Stabilizing | 0.999 | D | 0.571 | neutral | None | None | None | None | N |
| R/C | 0.6842 | likely_pathogenic | 0.4716 | ambiguous | -0.177 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| R/D | 0.9472 | likely_pathogenic | 0.8915 | pathogenic | -0.109 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/E | 0.7396 | likely_pathogenic | 0.6036 | pathogenic | -0.026 | Destabilizing | 0.997 | D | 0.612 | neutral | None | None | None | None | N |
| R/F | 0.9509 | likely_pathogenic | 0.8825 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/G | 0.7598 | likely_pathogenic | 0.5353 | ambiguous | -0.218 | Destabilizing | 1.0 | D | 0.567 | neutral | N | 0.509754957 | None | None | N |
| R/H | 0.4198 | ambiguous | 0.2937 | benign | -0.688 | Destabilizing | 0.999 | D | 0.746 | deleterious | None | None | None | None | N |
| R/I | 0.7899 | likely_pathogenic | 0.5784 | pathogenic | 0.572 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | N | 0.51481406 | None | None | N |
| R/K | 0.2129 | likely_benign | 0.141 | benign | -0.12 | Destabilizing | 0.972 | D | 0.505 | neutral | N | 0.417690158 | None | None | N |
| R/L | 0.7069 | likely_pathogenic | 0.5144 | ambiguous | 0.572 | Stabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | N |
| R/M | 0.8066 | likely_pathogenic | 0.6117 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/N | 0.9168 | likely_pathogenic | 0.8354 | pathogenic | 0.095 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/P | 0.8256 | likely_pathogenic | 0.6313 | pathogenic | 0.405 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| R/Q | 0.2808 | likely_benign | 0.1828 | benign | 0.031 | Stabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/S | 0.9216 | likely_pathogenic | 0.8123 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.618 | neutral | N | 0.499729965 | None | None | N |
| R/T | 0.8337 | likely_pathogenic | 0.6364 | pathogenic | -0.017 | Destabilizing | 1.0 | D | 0.617 | neutral | N | 0.499729965 | None | None | N |
| R/V | 0.8313 | likely_pathogenic | 0.656 | pathogenic | 0.405 | Stabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/W | 0.6754 | likely_pathogenic | 0.5 | ambiguous | -0.101 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| R/Y | 0.8624 | likely_pathogenic | 0.7484 | pathogenic | 0.284 | Stabilizing | 0.999 | D | 0.702 | prob.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.