Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19943 | 60052;60053;60054 | chr2:178592077;178592076;178592075 | chr2:179456804;179456803;179456802 |
| N2AB | 18302 | 55129;55130;55131 | chr2:178592077;178592076;178592075 | chr2:179456804;179456803;179456802 |
| N2A | 17375 | 52348;52349;52350 | chr2:178592077;178592076;178592075 | chr2:179456804;179456803;179456802 |
| N2B | 10878 | 32857;32858;32859 | chr2:178592077;178592076;178592075 | chr2:179456804;179456803;179456802 |
| Novex-1 | 11003 | 33232;33233;33234 | chr2:178592077;178592076;178592075 | chr2:179456804;179456803;179456802 |
| Novex-2 | 11070 | 33433;33434;33435 | chr2:178592077;178592076;178592075 | chr2:179456804;179456803;179456802 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/K | rs751863629  |
-0.187 | 0.999 | N | 0.702 | 0.418 | 0.472344434578 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 1.74561E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| E/K | rs751863629 |
-0.187 | 0.999 | N | 0.702 | 0.418 | 0.472344434578 | gnomAD-4.0.0 | 1.75228E-05 | None | None | None | None | N | None | 0 | 2.51935E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1784 | likely_benign | 0.2256 | benign | -0.5 | Destabilizing | 0.999 | D | 0.647 | neutral | N | 0.471569368 | None | None | N |
| E/C | 0.9124 | likely_pathogenic | 0.9478 | pathogenic | -0.024 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| E/D | 0.3013 | likely_benign | 0.3415 | ambiguous | -0.789 | Destabilizing | 0.999 | D | 0.594 | neutral | N | 0.49058913 | None | None | N |
| E/F | 0.8997 | likely_pathogenic | 0.9344 | pathogenic | -0.567 | Destabilizing | 1.0 | D | 0.628 | neutral | None | None | None | None | N |
| E/G | 0.3109 | likely_benign | 0.3866 | ambiguous | -0.758 | Destabilizing | 1.0 | D | 0.607 | neutral | N | 0.478334225 | None | None | N |
| E/H | 0.6881 | likely_pathogenic | 0.7675 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.634 | neutral | None | None | None | None | N |
| E/I | 0.4406 | ambiguous | 0.5684 | pathogenic | 0.161 | Stabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| E/K | 0.2535 | likely_benign | 0.3626 | ambiguous | -0.17 | Destabilizing | 0.999 | D | 0.702 | prob.neutral | N | 0.469331323 | None | None | N |
| E/L | 0.6254 | likely_pathogenic | 0.7328 | pathogenic | 0.161 | Stabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| E/M | 0.6284 | likely_pathogenic | 0.7232 | pathogenic | 0.564 | Stabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | N |
| E/N | 0.5388 | ambiguous | 0.6098 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| E/P | 0.4545 | ambiguous | 0.5341 | ambiguous | -0.037 | Destabilizing | 1.0 | D | 0.615 | neutral | None | None | None | None | N |
| E/Q | 0.2085 | likely_benign | 0.2564 | benign | -0.329 | Destabilizing | 1.0 | D | 0.688 | prob.neutral | D | 0.525042202 | None | None | N |
| E/R | 0.4179 | ambiguous | 0.546 | ambiguous | -0.081 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/S | 0.3458 | ambiguous | 0.415 | ambiguous | -0.589 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/T | 0.3371 | likely_benign | 0.4428 | ambiguous | -0.392 | Destabilizing | 1.0 | D | 0.639 | neutral | None | None | None | None | N |
| E/V | 0.2689 | likely_benign | 0.3632 | ambiguous | -0.037 | Destabilizing | 1.0 | D | 0.615 | neutral | N | 0.484664101 | None | None | N |
| E/W | 0.9702 | likely_pathogenic | 0.9819 | pathogenic | -0.513 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| E/Y | 0.8269 | likely_pathogenic | 0.8846 | pathogenic | -0.363 | Destabilizing | 1.0 | D | 0.607 | 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.