Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2494 | 7705;7706;7707 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
| N2AB | 2494 | 7705;7706;7707 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
| N2A | 2494 | 7705;7706;7707 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
| N2B | 2448 | 7567;7568;7569 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
| Novex-1 | 2448 | 7567;7568;7569 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
| Novex-2 | 2448 | 7567;7568;7569 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
| Novex-3 | 2494 | 7705;7706;7707 | chr2:178773576;178773575;178773574 | chr2:179638303;179638302;179638301 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs749215640  |
-0.606 | 0.984 | D | 0.545 | 0.328 | 0.55375338871 | gnomAD-2.1.1 | 7.08E-06 | None | None | None | None | N | None | 8.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs749215640 |
-0.606 | 0.984 | D | 0.545 | 0.328 | 0.55375338871 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs749215640 |
-0.606 | 0.984 | D | 0.545 | 0.328 | 0.55375338871 | gnomAD-4.0.0 | 2.47845E-06 | None | None | None | None | N | None | 2.67051E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69495E-06 | 0 | 0 |
| I/V | None | None | 0.004 | N | 0.125 | 0.086 | 0.601711566423 | gnomAD-4.0.0 | 9.54408E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.71403E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3245 | likely_benign | 0.352 | ambiguous | -1.391 | Destabilizing | 0.702 | D | 0.467 | neutral | None | None | None | None | N |
| I/C | 0.8211 | likely_pathogenic | 0.8284 | pathogenic | -0.844 | Destabilizing | 0.999 | D | 0.582 | neutral | None | None | None | None | N |
| I/D | 0.8623 | likely_pathogenic | 0.878 | pathogenic | -1.009 | Destabilizing | 0.996 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/E | 0.7687 | likely_pathogenic | 0.7932 | pathogenic | -1.041 | Destabilizing | 0.988 | D | 0.686 | prob.neutral | None | None | None | None | N |
| I/F | 0.2026 | likely_benign | 0.2168 | benign | -1.001 | Destabilizing | 0.968 | D | 0.501 | neutral | N | 0.504009105 | None | None | N |
| I/G | 0.7908 | likely_pathogenic | 0.8171 | pathogenic | -1.668 | Destabilizing | 0.988 | D | 0.656 | neutral | None | None | None | None | N |
| I/H | 0.7031 | likely_pathogenic | 0.7171 | pathogenic | -0.868 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/K | 0.64 | likely_pathogenic | 0.6758 | pathogenic | -1.07 | Destabilizing | 0.988 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/L | 0.1452 | likely_benign | 0.1492 | benign | -0.725 | Destabilizing | 0.437 | N | 0.231 | neutral | N | 0.475967614 | None | None | N |
| I/M | 0.1141 | likely_benign | 0.1204 | benign | -0.559 | Destabilizing | 0.984 | D | 0.545 | neutral | D | 0.548744629 | None | None | N |
| I/N | 0.4734 | ambiguous | 0.5005 | ambiguous | -0.862 | Destabilizing | 0.995 | D | 0.723 | prob.delet. | N | 0.504080339 | None | None | N |
| I/P | 0.932 | likely_pathogenic | 0.9433 | pathogenic | -0.915 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/Q | 0.6646 | likely_pathogenic | 0.6918 | pathogenic | -1.075 | Destabilizing | 0.996 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/R | 0.5535 | ambiguous | 0.5908 | pathogenic | -0.409 | Destabilizing | 0.988 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/S | 0.3985 | ambiguous | 0.4192 | ambiguous | -1.377 | Destabilizing | 0.984 | D | 0.619 | neutral | N | 0.45233174 | None | None | N |
| I/T | 0.2084 | likely_benign | 0.2318 | benign | -1.3 | Destabilizing | 0.896 | D | 0.505 | neutral | N | 0.460271373 | None | None | N |
| I/V | 0.0675 | likely_benign | 0.0713 | benign | -0.915 | Destabilizing | 0.004 | N | 0.125 | neutral | N | 0.41270556 | None | None | N |
| I/W | 0.8619 | likely_pathogenic | 0.8662 | pathogenic | -1.054 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6631 | likely_pathogenic | 0.6693 | pathogenic | -0.85 | Destabilizing | 0.988 | D | 0.603 | 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.