Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30946 | 93061;93062;93063 | chr2:178548790;178548789;178548788 | chr2:179413517;179413516;179413515 |
| N2AB | 29305 | 88138;88139;88140 | chr2:178548790;178548789;178548788 | chr2:179413517;179413516;179413515 |
| N2A | 28378 | 85357;85358;85359 | chr2:178548790;178548789;178548788 | chr2:179413517;179413516;179413515 |
| N2B | 21881 | 65866;65867;65868 | chr2:178548790;178548789;178548788 | chr2:179413517;179413516;179413515 |
| Novex-1 | 22006 | 66241;66242;66243 | chr2:178548790;178548789;178548788 | chr2:179413517;179413516;179413515 |
| Novex-2 | 22073 | 66442;66443;66444 | chr2:178548790;178548789;178548788 | chr2:179413517;179413516;179413515 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1462805478  |
-0.778 | 0.826 | N | 0.425 | 0.21 | 0.646368640663 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| F/L | rs1462805478 |
-0.778 | 0.826 | N | 0.425 | 0.21 | 0.646368640663 | gnomAD-4.0.0 | 1.36935E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79895E-06 | 0 | 0 |
| F/V | rs1462805478 |
-1.1 | 0.959 | N | 0.451 | 0.288 | 0.761389543597 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| F/V | rs1462805478 |
-1.1 | 0.959 | N | 0.451 | 0.288 | 0.761389543597 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/V | rs1462805478 |
-1.1 | 0.959 | N | 0.451 | 0.288 | 0.761389543597 | gnomAD-4.0.0 | 6.5722E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4702E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.7258 | likely_pathogenic | 0.6839 | pathogenic | -1.778 | Destabilizing | 0.863 | D | 0.483 | neutral | None | None | None | None | N |
| F/C | 0.398 | ambiguous | 0.3498 | ambiguous | -1.057 | Destabilizing | 0.999 | D | 0.581 | neutral | N | 0.518743453 | None | None | N |
| F/D | 0.8689 | likely_pathogenic | 0.8396 | pathogenic | 0.119 | Stabilizing | 0.939 | D | 0.547 | neutral | None | None | None | None | N |
| F/E | 0.8703 | likely_pathogenic | 0.8375 | pathogenic | 0.224 | Stabilizing | 0.759 | D | 0.495 | neutral | None | None | None | None | N |
| F/G | 0.8582 | likely_pathogenic | 0.8293 | pathogenic | -2.091 | Highly Destabilizing | 0.969 | D | 0.513 | neutral | None | None | None | None | N |
| F/H | 0.4597 | ambiguous | 0.4377 | ambiguous | -0.187 | Destabilizing | 0.046 | N | 0.299 | neutral | None | None | None | None | N |
| F/I | 0.4335 | ambiguous | 0.4196 | ambiguous | -0.849 | Destabilizing | 0.986 | D | 0.448 | neutral | N | 0.482312195 | None | None | N |
| F/K | 0.861 | likely_pathogenic | 0.8181 | pathogenic | -0.9 | Destabilizing | 0.884 | D | 0.519 | neutral | None | None | None | None | N |
| F/L | 0.8973 | likely_pathogenic | 0.8755 | pathogenic | -0.849 | Destabilizing | 0.826 | D | 0.425 | neutral | N | 0.490671417 | None | None | N |
| F/M | 0.6099 | likely_pathogenic | 0.5849 | pathogenic | -0.771 | Destabilizing | 0.997 | D | 0.499 | neutral | None | None | None | None | N |
| F/N | 0.6416 | likely_pathogenic | 0.617 | pathogenic | -1.079 | Destabilizing | 0.939 | D | 0.554 | neutral | None | None | None | None | N |
| F/P | 0.9856 | likely_pathogenic | 0.9805 | pathogenic | -1.15 | Destabilizing | 0.997 | D | 0.59 | neutral | None | None | None | None | N |
| F/Q | 0.7174 | likely_pathogenic | 0.6639 | pathogenic | -1.024 | Destabilizing | 0.2 | N | 0.379 | neutral | None | None | None | None | N |
| F/R | 0.7078 | likely_pathogenic | 0.6394 | pathogenic | -0.4 | Destabilizing | 0.939 | D | 0.554 | neutral | None | None | None | None | N |
| F/S | 0.5331 | ambiguous | 0.4822 | ambiguous | -1.941 | Destabilizing | 0.92 | D | 0.511 | neutral | N | 0.449688799 | None | None | N |
| F/T | 0.6724 | likely_pathogenic | 0.6235 | pathogenic | -1.74 | Destabilizing | 0.969 | D | 0.537 | neutral | None | None | None | None | N |
| F/V | 0.4077 | ambiguous | 0.3775 | ambiguous | -1.15 | Destabilizing | 0.959 | D | 0.451 | neutral | N | 0.484553521 | None | None | N |
| F/W | 0.5465 | ambiguous | 0.5222 | ambiguous | 0.069 | Stabilizing | 0.999 | D | 0.499 | neutral | None | None | None | None | N |
| F/Y | 0.1508 | likely_benign | 0.1536 | benign | -0.211 | Destabilizing | 0.92 | D | 0.413 | neutral | N | 0.470181502 | 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.