Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8294 | 25105;25106;25107 | chr2:178718126;178718125;178718124 | chr2:179582853;179582852;179582851 |
| N2AB | 7977 | 24154;24155;24156 | chr2:178718126;178718125;178718124 | chr2:179582853;179582852;179582851 |
| N2A | 7050 | 21373;21374;21375 | chr2:178718126;178718125;178718124 | chr2:179582853;179582852;179582851 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs72648982  |
-0.125 | 0.153 | N | 0.552 | 0.182 | None | gnomAD-2.1.1 | 2.17258E-02 | None | None | None | None | I | None | 5.83368E-03 | 1.12633E-02 | None | 5.20309E-02 | 0 | None | 1.77859E-02 | None | 1.87732E-02 | 2.9633E-02 | 2.76134E-02 |
| R/G | rs72648982 |
-0.125 | 0.153 | N | 0.552 | 0.182 | None | gnomAD-3.1.2 | 2.06025E-02 | None | None | None | None | I | None | 5.4298E-03 | 2.14772E-02 | 3.94737E-02 | 5.07205E-02 | 1.92604E-04 | None | 1.66604E-02 | 3.48101E-02 | 2.98018E-02 | 1.82119E-02 | 3.15186E-02 |
| R/G | rs72648982 |
-0.125 | 0.153 | N | 0.552 | 0.182 | None | 1000 genomes | 1.21805E-02 | None | None | None | None | I | None | 2.3E-03 | 1.3E-02 | None | None | 1E-03 | 2.78E-02 | None | None | None | 2.04E-02 | None |
| R/G | rs72648982 |
-0.125 | 0.153 | N | 0.552 | 0.182 | None | gnomAD-4.0.0 | 2.73513E-02 | None | None | None | None | I | None | 5.43855E-03 | 1.49485E-02 | None | 5.41326E-02 | 1.11428E-04 | None | 1.91762E-02 | 5.18494E-02 | 3.05717E-02 | 1.88524E-02 | 2.95097E-02 |
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 | 0.3729 | ambiguous | 0.4935 | ambiguous | -0.509 | Destabilizing | 0.047 | N | 0.502 | neutral | None | None | None | None | I |
| R/C | 0.273 | likely_benign | 0.3009 | benign | -0.455 | Destabilizing | 0.951 | D | 0.495 | neutral | None | None | None | None | I |
| R/D | 0.6331 | likely_pathogenic | 0.7537 | pathogenic | -0.141 | Destabilizing | 0.001 | N | 0.341 | neutral | None | None | None | None | I |
| R/E | 0.3433 | ambiguous | 0.4704 | ambiguous | -0.059 | Destabilizing | None | N | 0.194 | neutral | None | None | None | None | I |
| R/F | 0.5959 | likely_pathogenic | 0.6877 | pathogenic | -0.613 | Destabilizing | 0.674 | D | 0.524 | neutral | None | None | None | None | I |
| R/G | 0.2614 | likely_benign | 0.2215 | benign | -0.759 | Destabilizing | 0.153 | N | 0.552 | neutral | N | 0.488846335 | None | None | I |
| R/H | 0.1021 | likely_benign | 0.1157 | benign | -1.182 | Destabilizing | 0.415 | N | 0.574 | neutral | None | None | None | None | I |
| R/I | 0.2578 | likely_benign | 0.3346 | benign | 0.138 | Stabilizing | 0.348 | N | 0.545 | neutral | N | 0.4834388 | None | None | I |
| R/K | 0.0882 | likely_benign | 0.093 | benign | -0.572 | Destabilizing | None | N | 0.17 | neutral | N | 0.432777907 | None | None | I |
| R/L | 0.2837 | likely_benign | 0.3626 | ambiguous | 0.138 | Stabilizing | 0.091 | N | 0.601 | neutral | None | None | None | None | I |
| R/M | 0.2676 | likely_benign | 0.3431 | ambiguous | -0.098 | Destabilizing | 0.683 | D | 0.55 | neutral | None | None | None | None | I |
| R/N | 0.4504 | ambiguous | 0.5793 | pathogenic | -0.064 | Destabilizing | 0.194 | N | 0.505 | neutral | None | None | None | None | I |
| R/P | 0.8738 | likely_pathogenic | 0.9111 | pathogenic | -0.056 | Destabilizing | 0.327 | N | 0.611 | neutral | None | None | None | None | I |
| R/Q | 0.1009 | likely_benign | 0.1165 | benign | -0.283 | Destabilizing | 0.081 | N | 0.525 | neutral | None | None | None | None | I |
| R/S | 0.3657 | ambiguous | 0.5038 | ambiguous | -0.675 | Destabilizing | 0.036 | N | 0.521 | neutral | N | 0.453921183 | None | None | I |
| R/T | 0.1656 | likely_benign | 0.2364 | benign | -0.439 | Destabilizing | 0.153 | N | 0.57 | neutral | N | 0.416424374 | None | None | I |
| R/V | 0.3292 | likely_benign | 0.4164 | ambiguous | -0.056 | Destabilizing | 0.067 | N | 0.599 | neutral | None | None | None | None | I |
| R/W | 0.2561 | likely_benign | 0.2859 | benign | -0.426 | Destabilizing | 0.967 | D | 0.519 | neutral | None | None | None | None | I |
| R/Y | 0.4849 | ambiguous | 0.5533 | ambiguous | -0.075 | Destabilizing | 0.674 | D | 0.543 | neutral | 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.