Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8497 | 25714;25715;25716 | chr2:178717245;178717244;178717243 | chr2:179581972;179581971;179581970 |
| N2AB | 8180 | 24763;24764;24765 | chr2:178717245;178717244;178717243 | chr2:179581972;179581971;179581970 |
| N2A | 7253 | 21982;21983;21984 | chr2:178717245;178717244;178717243 | chr2:179581972;179581971;179581970 |
| 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/C | rs369517119  |
-0.337 | 1.0 | N | 0.345 | 0.441 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 6.46E-05 | 2.9E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 4.43E-05 | 0 |
| R/C | rs369517119 |
-0.337 | 1.0 | N | 0.345 | 0.441 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92827E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs369517119 |
-0.337 | 1.0 | N | 0.345 | 0.441 | None | gnomAD-4.0.0 | 1.11553E-05 | None | None | None | None | N | None | 1.33486E-05 | 1.667E-05 | None | 0 | 2.22846E-05 | None | 3.1248E-05 | 0 | 1.01722E-05 | 1.09794E-05 | 0 |
| R/H | rs149855485 |
-0.757 | 0.99 | N | 0.374 | 0.192 | None | gnomAD-2.1.1 | 3.44631E-03 | None | None | None | None | N | None | 1.23977E-04 | 7.6392E-04 | None | 1.06321E-03 | 1.02543E-04 | None | 2.18613E-02 | None | 4E-05 | 1.8021E-03 | 3.08989E-03 |
| R/H | rs149855485 |
-0.757 | 0.99 | N | 0.374 | 0.192 | None | gnomAD-3.1.2 | 1.76827E-03 | None | None | None | None | N | None | 1.68943E-04 | 1.70291E-03 | 0 | 8.64055E-04 | 1.92604E-04 | None | 0 | 0 | 1.67637E-03 | 2.3849E-02 | 1.43541E-03 |
| R/H | rs149855485 |
-0.757 | 0.99 | N | 0.374 | 0.192 | None | 1000 genomes | 5.99042E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 2E-03 | None | None | None | 2.76E-02 | None |
| R/H | rs149855485 |
-0.757 | 0.99 | N | 0.374 | 0.192 | None | gnomAD-4.0.0 | 2.20866E-03 | None | None | None | None | N | None | 2.5332E-04 | 9.49937E-04 | None | 8.44709E-04 | 8.91504E-05 | None | 6.2498E-05 | 4.12405E-03 | 1.12914E-03 | 2.12259E-02 | 2.64135E-03 |
| R/S | rs369517119 |
None | 0.881 | N | 0.385 | 0.235 | 0.373357554552 | gnomAD-4.0.0 | 6.84274E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99546E-07 | 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 | 0.8933 | likely_pathogenic | 0.8307 | pathogenic | 0.124 | Stabilizing | 0.762 | D | 0.383 | neutral | None | None | None | None | N |
| R/C | 0.5592 | ambiguous | 0.4865 | ambiguous | -0.163 | Destabilizing | 1.0 | D | 0.345 | neutral | N | 0.490633988 | None | None | N |
| R/D | 0.9756 | likely_pathogenic | 0.9597 | pathogenic | -0.273 | Destabilizing | 0.024 | N | 0.28 | neutral | None | None | None | None | N |
| R/E | 0.9008 | likely_pathogenic | 0.8547 | pathogenic | -0.224 | Destabilizing | 0.325 | N | 0.344 | neutral | None | None | None | None | N |
| R/F | 0.8331 | likely_pathogenic | 0.7851 | pathogenic | -0.162 | Destabilizing | 0.956 | D | 0.359 | neutral | None | None | None | None | N |
| R/G | 0.792 | likely_pathogenic | 0.7099 | pathogenic | -0.03 | Destabilizing | 0.937 | D | 0.399 | neutral | N | 0.494810587 | None | None | N |
| R/H | 0.2535 | likely_benign | 0.2165 | benign | -0.567 | Destabilizing | 0.99 | D | 0.374 | neutral | N | 0.491578281 | None | None | N |
| R/I | 0.6873 | likely_pathogenic | 0.594 | pathogenic | 0.486 | Stabilizing | 0.091 | N | 0.343 | neutral | None | None | None | None | N |
| R/K | 0.2441 | likely_benign | 0.1958 | benign | -0.074 | Destabilizing | 0.16 | N | 0.359 | neutral | None | None | None | None | N |
| R/L | 0.5704 | likely_pathogenic | 0.5101 | ambiguous | 0.486 | Stabilizing | 0.56 | D | 0.371 | neutral | N | 0.493463793 | None | None | N |
| R/M | 0.7579 | likely_pathogenic | 0.6824 | pathogenic | -0.023 | Destabilizing | 0.958 | D | 0.367 | neutral | None | None | None | None | N |
| R/N | 0.9451 | likely_pathogenic | 0.9177 | pathogenic | 0.01 | Stabilizing | 0.886 | D | 0.363 | neutral | None | None | None | None | N |
| R/P | 0.8633 | likely_pathogenic | 0.8083 | pathogenic | 0.384 | Stabilizing | 0.997 | D | 0.341 | neutral | N | 0.475782109 | None | None | N |
| R/Q | 0.3092 | likely_benign | 0.2733 | benign | -0.013 | Destabilizing | 0.34 | N | 0.205 | neutral | None | None | None | None | N |
| R/S | 0.9095 | likely_pathogenic | 0.8692 | pathogenic | -0.146 | Destabilizing | 0.881 | D | 0.385 | neutral | N | 0.460484583 | None | None | N |
| R/T | 0.8293 | likely_pathogenic | 0.74 | pathogenic | 0.014 | Stabilizing | 0.094 | N | 0.244 | neutral | None | None | None | None | N |
| R/V | 0.7714 | likely_pathogenic | 0.6988 | pathogenic | 0.384 | Stabilizing | 0.538 | D | 0.377 | neutral | None | None | None | None | N |
| R/W | 0.3705 | ambiguous | 0.3342 | benign | -0.347 | Destabilizing | 0.999 | D | 0.381 | neutral | None | None | None | None | N |
| R/Y | 0.7261 | likely_pathogenic | 0.679 | pathogenic | 0.066 | Stabilizing | 0.985 | D | 0.355 | 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.