Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2108 | 6547;6548;6549 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
| N2AB | 2108 | 6547;6548;6549 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
| N2A | 2108 | 6547;6548;6549 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
| N2B | 2062 | 6409;6410;6411 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
| Novex-1 | 2062 | 6409;6410;6411 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
| Novex-2 | 2062 | 6409;6410;6411 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
| Novex-3 | 2108 | 6547;6548;6549 | chr2:178775542;178775541;178775540 | chr2:179640269;179640268;179640267 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs762999586  |
0.109 | 1.0 | N | 0.635 | 0.502 | None | gnomAD-2.1.1 | 2.84E-05 | None | None | None | None | N | None | 0 | 8.48E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.89E-05 | 0 |
| E/K | rs762999586 |
0.109 | 1.0 | N | 0.635 | 0.502 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| E/K | rs762999586 |
0.109 | 1.0 | N | 0.635 | 0.502 | None | gnomAD-4.0.0 | 2.29271E-05 | None | None | None | None | N | None | 0 | 1.0005E-04 | None | 0 | 0 | None | 1.56211E-05 | 1.64366E-04 | 2.03396E-05 | 1.09796E-05 | 6.40225E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.2265 | likely_benign | 0.2799 | benign | -0.379 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | N | 0.505349498 | None | None | N |
| E/C | 0.9289 | likely_pathogenic | 0.9488 | pathogenic | -0.215 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| E/D | 0.243 | likely_benign | 0.2839 | benign | -0.405 | Destabilizing | 0.999 | D | 0.515 | neutral | N | 0.513657448 | None | None | N |
| E/F | 0.8251 | likely_pathogenic | 0.8621 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| E/G | 0.4132 | ambiguous | 0.5131 | ambiguous | -0.614 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | D | 0.626343205 | None | None | N |
| E/H | 0.6049 | likely_pathogenic | 0.6665 | pathogenic | 0.007 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| E/I | 0.37 | ambiguous | 0.4162 | ambiguous | 0.219 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| E/K | 0.2707 | likely_benign | 0.317 | benign | -0.009 | Destabilizing | 1.0 | D | 0.635 | neutral | N | 0.512415992 | None | None | N |
| E/L | 0.4947 | ambiguous | 0.5691 | pathogenic | 0.219 | Stabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| E/M | 0.5671 | likely_pathogenic | 0.6235 | pathogenic | 0.244 | Stabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| E/N | 0.3931 | ambiguous | 0.4526 | ambiguous | -0.26 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| E/P | 0.9526 | likely_pathogenic | 0.9735 | pathogenic | 0.041 | Stabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| E/Q | 0.1889 | likely_benign | 0.2181 | benign | -0.196 | Destabilizing | 1.0 | D | 0.647 | neutral | N | 0.500149132 | None | None | N |
| E/R | 0.4017 | ambiguous | 0.47 | ambiguous | 0.28 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| E/S | 0.2914 | likely_benign | 0.3478 | ambiguous | -0.473 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | N |
| E/T | 0.292 | likely_benign | 0.3467 | ambiguous | -0.287 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| E/V | 0.2316 | likely_benign | 0.2688 | benign | 0.041 | Stabilizing | 1.0 | D | 0.769 | deleterious | D | 0.535056995 | None | None | N |
| E/W | 0.9626 | likely_pathogenic | 0.9749 | pathogenic | 0.015 | Stabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| E/Y | 0.773 | likely_pathogenic | 0.8238 | pathogenic | 0.09 | Stabilizing | 1.0 | D | 0.77 | 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.