Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33466 | 100621;100622;100623 | chr2:178536351;178536350;178536349 | chr2:179401078;179401077;179401076 |
| N2AB | 31825 | 95698;95699;95700 | chr2:178536351;178536350;178536349 | chr2:179401078;179401077;179401076 |
| N2A | 30898 | 92917;92918;92919 | chr2:178536351;178536350;178536349 | chr2:179401078;179401077;179401076 |
| N2B | 24401 | 73426;73427;73428 | chr2:178536351;178536350;178536349 | chr2:179401078;179401077;179401076 |
| Novex-1 | 24526 | 73801;73802;73803 | chr2:178536351;178536350;178536349 | chr2:179401078;179401077;179401076 |
| Novex-2 | 24593 | 74002;74003;74004 | chr2:178536351;178536350;178536349 | chr2:179401078;179401077;179401076 |
| 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 | rs371908649  |
-1.698 | 1.0 | D | 0.821 | 0.685 | None | gnomAD-2.1.1 | 1.42913E-04 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 1.69318E-03 | None | 1.63441E-04 | None | 0 | 7.82E-06 | 0 |
| R/C | rs371908649 |
-1.698 | 1.0 | D | 0.821 | 0.685 | None | gnomAD-3.1.2 | 7.89E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 1.15607E-03 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 4.78927E-04 |
| R/C | rs371908649 |
-1.698 | 1.0 | D | 0.821 | 0.685 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| R/C | rs371908649 |
-1.698 | 1.0 | D | 0.821 | 0.685 | None | gnomAD-4.0.0 | 3.28441E-05 | None | None | None | None | N | None | 6.66347E-05 | 0 | None | 3.37815E-05 | 6.01819E-04 | None | 0 | 0 | 5.08585E-06 | 1.31761E-04 | 3.20174E-05 |
| R/H | None | -2.565 | 1.0 | D | 0.804 | 0.711 | None | gnomAD-2.1.1 | 6.79E-05 | None | None | None | None | N | None | 1.23998E-04 | 2.55044E-04 | None | 0 | 5.13E-05 | None | 0 | None | 0 | 3.91E-05 | 1.40805E-04 |
| R/H | None | -2.565 | 1.0 | D | 0.804 | 0.711 | None | gnomAD-3.1.2 | 1.97148E-04 | None | None | None | None | N | None | 1.44732E-04 | 1.4396E-03 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | None | -2.565 | 1.0 | D | 0.804 | 0.711 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | None | -2.565 | 1.0 | D | 0.804 | 0.711 | None | gnomAD-4.0.0 | 7.12636E-05 | None | None | None | None | N | None | 1.46588E-04 | 5.49945E-04 | None | 0 | 4.45871E-05 | None | 0 | 0 | 4.66194E-05 | 0 | 2.24093E-04 |
| R/L | rs189626540 |
-1.26 | 1.0 | N | 0.718 | 0.686 | 0.696815536761 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 9.67E-05 | 0 | None | 0 | None | 0 | 1.56E-05 | 1.40805E-04 |
| R/L | rs189626540 |
-1.26 | 1.0 | N | 0.718 | 0.686 | 0.696815536761 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/L | rs189626540 |
-1.26 | 1.0 | N | 0.718 | 0.686 | 0.696815536761 | gnomAD-4.0.0 | 4.3381E-06 | None | None | None | None | N | None | 1.33479E-05 | 1.66706E-05 | None | 3.37838E-05 | 0 | None | 0 | 0 | 2.54286E-06 | 0 | 1.60123E-05 |
| R/P | rs189626540 |
-1.803 | 1.0 | D | 0.819 | 0.696 | 0.650727440417 | 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/P | rs189626540 |
-1.803 | 1.0 | D | 0.819 | 0.696 | 0.650727440417 | gnomAD-4.0.0 | 6.84257E-07 | None | None | None | None | N | None | 0 | 2.23694E-05 | None | 0 | 0 | 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 | 0.9792 | likely_pathogenic | 0.968 | pathogenic | -2.397 | Highly Destabilizing | 0.999 | D | 0.604 | neutral | None | None | None | None | N |
| R/C | 0.6312 | likely_pathogenic | 0.5292 | ambiguous | -2.016 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | D | 0.534158381 | None | None | N |
| R/D | 0.9985 | likely_pathogenic | 0.998 | pathogenic | -1.744 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| R/E | 0.9765 | likely_pathogenic | 0.968 | pathogenic | -1.505 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| R/F | 0.9823 | likely_pathogenic | 0.9761 | pathogenic | -1.436 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| R/G | 0.9809 | likely_pathogenic | 0.9743 | pathogenic | -2.717 | Highly Destabilizing | 1.0 | D | 0.718 | prob.delet. | D | 0.545425781 | None | None | N |
| R/H | 0.4416 | ambiguous | 0.357 | ambiguous | -2.04 | Highly Destabilizing | 1.0 | D | 0.804 | deleterious | D | 0.545679271 | None | None | N |
| R/I | 0.939 | likely_pathogenic | 0.9273 | pathogenic | -1.424 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| R/K | 0.5403 | ambiguous | 0.4506 | ambiguous | -1.13 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| R/L | 0.906 | likely_pathogenic | 0.8741 | pathogenic | -1.424 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | N | 0.511445771 | None | None | N |
| R/M | 0.9618 | likely_pathogenic | 0.9381 | pathogenic | -1.853 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| R/N | 0.9931 | likely_pathogenic | 0.9893 | pathogenic | -1.732 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| R/P | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -1.745 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.54593276 | None | None | N |
| R/Q | 0.5421 | ambiguous | 0.453 | ambiguous | -1.508 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| R/S | 0.9895 | likely_pathogenic | 0.9849 | pathogenic | -2.491 | Highly Destabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.512669857 | None | None | N |
| R/T | 0.9799 | likely_pathogenic | 0.972 | pathogenic | -2.044 | Highly Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | N |
| R/V | 0.9588 | likely_pathogenic | 0.9433 | pathogenic | -1.745 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/W | 0.8265 | likely_pathogenic | 0.8153 | pathogenic | -0.942 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| R/Y | 0.9547 | likely_pathogenic | 0.9371 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.847 | 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.