Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3054 | 9385;9386;9387 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
| N2AB | 3054 | 9385;9386;9387 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
| N2A | 3054 | 9385;9386;9387 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
| N2B | 3008 | 9247;9248;9249 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
| Novex-1 | 3008 | 9247;9248;9249 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
| Novex-2 | 3008 | 9247;9248;9249 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
| Novex-3 | 3054 | 9385;9386;9387 | chr2:178768676;178768675;178768674 | chr2:179633403;179633402;179633401 |
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 | rs397517779  |
None | 0.999 | N | 0.511 | 0.426 | 0.190952846119 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.63345E-04 |
| E/K | rs397517779 |
None | 0.999 | N | 0.511 | 0.426 | 0.190952846119 | gnomAD-4.0.0 | 4.77204E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71308E-06 | 0 | 3.02188E-05 |
| E/Q | None | None | 1.0 | N | 0.532 | 0.29 | 0.110078149338 | gnomAD-4.0.0 | 3.18136E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.82393E-04 | 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 | 0.6734 | likely_pathogenic | 0.5881 | pathogenic | -0.425 | Destabilizing | 0.999 | D | 0.531 | neutral | N | 0.399037913 | None | None | N |
| E/C | 0.9918 | likely_pathogenic | 0.9893 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| E/D | 0.6286 | likely_pathogenic | 0.522 | ambiguous | -0.46 | Destabilizing | 0.999 | D | 0.397 | neutral | N | 0.340488711 | None | None | N |
| E/F | 0.9863 | likely_pathogenic | 0.9798 | pathogenic | -0.15 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| E/G | 0.7742 | likely_pathogenic | 0.6983 | pathogenic | -0.664 | Destabilizing | 1.0 | D | 0.525 | neutral | N | 0.400948532 | None | None | N |
| E/H | 0.9384 | likely_pathogenic | 0.9165 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| E/I | 0.92 | likely_pathogenic | 0.8779 | pathogenic | 0.183 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| E/K | 0.7082 | likely_pathogenic | 0.6226 | pathogenic | 0.139 | Stabilizing | 0.999 | D | 0.511 | neutral | N | 0.337406458 | None | None | N |
| E/L | 0.9305 | likely_pathogenic | 0.89 | pathogenic | 0.183 | Stabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | N |
| E/M | 0.9163 | likely_pathogenic | 0.8779 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.624 | neutral | None | None | None | None | N |
| E/N | 0.8648 | likely_pathogenic | 0.7998 | pathogenic | -0.232 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | N |
| E/P | 0.996 | likely_pathogenic | 0.9926 | pathogenic | 0.001 | Stabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | N |
| E/Q | 0.5403 | ambiguous | 0.4744 | ambiguous | -0.17 | Destabilizing | 1.0 | D | 0.532 | neutral | N | 0.342597471 | None | None | N |
| E/R | 0.8265 | likely_pathogenic | 0.7736 | pathogenic | 0.421 | Stabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | N |
| E/S | 0.769 | likely_pathogenic | 0.6915 | pathogenic | -0.421 | Destabilizing | 0.999 | D | 0.537 | neutral | None | None | None | None | N |
| E/T | 0.8036 | likely_pathogenic | 0.7177 | pathogenic | -0.224 | Destabilizing | 1.0 | D | 0.559 | neutral | None | None | None | None | N |
| E/V | 0.7654 | likely_pathogenic | 0.6768 | pathogenic | 0.001 | Stabilizing | 1.0 | D | 0.576 | neutral | N | 0.399816257 | None | None | N |
| E/W | 0.9962 | likely_pathogenic | 0.9944 | pathogenic | 0.041 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| E/Y | 0.9781 | likely_pathogenic | 0.9692 | pathogenic | 0.101 | Stabilizing | 1.0 | D | 0.631 | 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.