Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14019 | 42280;42281;42282 | chr2:178634819;178634818;178634817 | chr2:179499546;179499545;179499544 |
| N2AB | 12378 | 37357;37358;37359 | chr2:178634819;178634818;178634817 | chr2:179499546;179499545;179499544 |
| N2A | 11451 | 34576;34577;34578 | chr2:178634819;178634818;178634817 | chr2:179499546;179499545;179499544 |
| N2B | 4954 | 15085;15086;15087 | chr2:178634819;178634818;178634817 | chr2:179499546;179499545;179499544 |
| Novex-1 | 5079 | 15460;15461;15462 | chr2:178634819;178634818;178634817 | chr2:179499546;179499545;179499544 |
| Novex-2 | 5146 | 15661;15662;15663 | chr2:178634819;178634818;178634817 | chr2:179499546;179499545;179499544 |
| 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 | rs763499817  |
-1.838 | 1.0 | N | 0.858 | 0.419 | 0.349870743963 | gnomAD-2.1.1 | 8.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.79E-05 | 0 |
| R/C | rs763499817 |
-1.838 | 1.0 | N | 0.858 | 0.419 | 0.349870743963 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs763499817 |
-1.838 | 1.0 | N | 0.858 | 0.419 | 0.349870743963 | gnomAD-4.0.0 | 1.055E-05 | None | None | None | None | N | None | 0 | 1.67926E-05 | None | 0 | 0 | None | 0 | 0 | 1.18741E-05 | 2.21136E-05 | 0 |
| R/H | rs374683153 |
-2.104 | 1.0 | N | 0.785 | 0.405 | None | gnomAD-2.1.1 | 2.01348E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.70148E-03 | None | 0 | 3.14E-05 | 1.41283E-04 |
| R/H | rs374683153 |
-2.104 | 1.0 | N | 0.785 | 0.405 | None | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.65975E-03 | 0 |
| R/H | rs374683153 |
-2.104 | 1.0 | N | 0.785 | 0.405 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| R/H | rs374683153 |
-2.104 | 1.0 | N | 0.785 | 0.405 | None | gnomAD-4.0.0 | 1.27817E-04 | None | None | None | None | N | None | 5.34388E-05 | 0 | None | 0 | 0 | None | 1.56318E-05 | 0 | 8.48129E-06 | 2.04461E-03 | 9.61754E-05 |
| R/P | rs374683153 |
-1.527 | 1.0 | N | 0.846 | 0.482 | 0.292787519742 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| R/P | rs374683153 |
-1.527 | 1.0 | N | 0.846 | 0.482 | 0.292787519742 | gnomAD-4.0.0 | 6.8515E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00025E-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 | 0.9552 | likely_pathogenic | 0.9394 | pathogenic | -2.417 | Highly Destabilizing | 0.998 | D | 0.649 | prob.neutral | None | None | None | None | N |
| R/C | 0.6068 | likely_pathogenic | 0.5264 | ambiguous | -2.208 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | N | 0.468210823 | None | None | N |
| R/D | 0.9911 | likely_pathogenic | 0.9896 | pathogenic | -1.379 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | N |
| R/E | 0.9554 | likely_pathogenic | 0.9413 | pathogenic | -1.127 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | N |
| R/F | 0.9587 | likely_pathogenic | 0.9451 | pathogenic | -1.58 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| R/G | 0.945 | likely_pathogenic | 0.9266 | pathogenic | -2.781 | Highly Destabilizing | 1.0 | D | 0.782 | deleterious | N | 0.467975708 | None | None | N |
| R/H | 0.4443 | ambiguous | 0.3447 | ambiguous | -2.286 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.429888784 | None | None | N |
| R/I | 0.8264 | likely_pathogenic | 0.7903 | pathogenic | -1.33 | Destabilizing | 0.999 | D | 0.839 | deleterious | None | None | None | None | N |
| R/K | 0.6397 | likely_pathogenic | 0.5537 | ambiguous | -1.213 | Destabilizing | 0.995 | D | 0.579 | neutral | None | None | None | None | N |
| R/L | 0.8221 | likely_pathogenic | 0.8019 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.782 | deleterious | N | 0.462978878 | None | None | N |
| R/M | 0.9135 | likely_pathogenic | 0.8889 | pathogenic | -1.755 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| R/N | 0.9618 | likely_pathogenic | 0.9482 | pathogenic | -1.62 | Destabilizing | 0.999 | D | 0.804 | deleterious | None | None | None | None | N |
| R/P | 0.9963 | likely_pathogenic | 0.9958 | pathogenic | -1.686 | Destabilizing | 1.0 | D | 0.846 | deleterious | N | 0.469049568 | None | None | N |
| R/Q | 0.5655 | likely_pathogenic | 0.4354 | ambiguous | -1.447 | Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| R/S | 0.9721 | likely_pathogenic | 0.9574 | pathogenic | -2.596 | Highly Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.428758949 | None | None | N |
| R/T | 0.9389 | likely_pathogenic | 0.9044 | pathogenic | -2.104 | Highly Destabilizing | 0.999 | D | 0.805 | deleterious | None | None | None | None | N |
| R/V | 0.8714 | likely_pathogenic | 0.8493 | pathogenic | -1.686 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | N |
| R/W | 0.7481 | likely_pathogenic | 0.6917 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/Y | 0.797 | likely_pathogenic | 0.7725 | pathogenic | -0.945 | Destabilizing | 0.999 | D | 0.869 | 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.