Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33512 | 100759;100760;100761 | chr2:178536213;178536212;178536211 | chr2:179400940;179400939;179400938 |
| N2AB | 31871 | 95836;95837;95838 | chr2:178536213;178536212;178536211 | chr2:179400940;179400939;179400938 |
| N2A | 30944 | 93055;93056;93057 | chr2:178536213;178536212;178536211 | chr2:179400940;179400939;179400938 |
| N2B | 24447 | 73564;73565;73566 | chr2:178536213;178536212;178536211 | chr2:179400940;179400939;179400938 |
| Novex-1 | 24572 | 73939;73940;73941 | chr2:178536213;178536212;178536211 | chr2:179400940;179400939;179400938 |
| Novex-2 | 24639 | 74140;74141;74142 | chr2:178536213;178536212;178536211 | chr2:179400940;179400939;179400938 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/Y | rs778965506  |
-0.69 | 0.844 | N | 0.434 | 0.413 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.5E-05 | 0 |
| N/Y | rs778965506 |
-0.69 | 0.844 | N | 0.434 | 0.413 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| N/Y | rs778965506 |
-0.69 | 0.844 | N | 0.434 | 0.413 | None | gnomAD-4.0.0 | 5.45485E-05 | None | None | None | None | N | None | 1.33483E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.29088E-05 | 0 | 1.6019E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4098 | ambiguous | 0.2935 | benign | -0.603 | Destabilizing | 0.011 | N | 0.397 | neutral | None | None | None | None | N |
| N/C | 0.5948 | likely_pathogenic | 0.4574 | ambiguous | 0.219 | Stabilizing | 0.979 | D | 0.448 | neutral | None | None | None | None | N |
| N/D | 0.3919 | ambiguous | 0.259 | benign | 0.157 | Stabilizing | 0.11 | N | 0.301 | neutral | N | 0.476760757 | None | None | N |
| N/E | 0.8266 | likely_pathogenic | 0.7039 | pathogenic | 0.139 | Stabilizing | 0.353 | N | 0.271 | neutral | None | None | None | None | N |
| N/F | 0.8555 | likely_pathogenic | 0.7687 | pathogenic | -0.924 | Destabilizing | 0.936 | D | 0.429 | neutral | None | None | None | None | N |
| N/G | 0.5399 | ambiguous | 0.3878 | ambiguous | -0.79 | Destabilizing | 0.407 | N | 0.279 | neutral | None | None | None | None | N |
| N/H | 0.2609 | likely_benign | 0.2081 | benign | -0.769 | Destabilizing | 0.004 | N | 0.261 | neutral | N | 0.506203348 | None | None | N |
| N/I | 0.5304 | ambiguous | 0.4249 | ambiguous | -0.187 | Destabilizing | 0.669 | D | 0.447 | neutral | N | 0.488099093 | None | None | N |
| N/K | 0.8148 | likely_pathogenic | 0.696 | pathogenic | 0.17 | Stabilizing | 0.02 | N | 0.218 | neutral | N | 0.506486231 | None | None | N |
| N/L | 0.522 | ambiguous | 0.4217 | ambiguous | -0.187 | Destabilizing | 0.277 | N | 0.421 | neutral | None | None | None | None | N |
| N/M | 0.609 | likely_pathogenic | 0.4967 | ambiguous | 0.308 | Stabilizing | 0.984 | D | 0.395 | neutral | None | None | None | None | N |
| N/P | 0.6285 | likely_pathogenic | 0.5097 | ambiguous | -0.299 | Destabilizing | 0.538 | D | 0.44 | neutral | None | None | None | None | N |
| N/Q | 0.6759 | likely_pathogenic | 0.5594 | ambiguous | -0.431 | Destabilizing | 0.728 | D | 0.353 | neutral | None | None | None | None | N |
| N/R | 0.8216 | likely_pathogenic | 0.7327 | pathogenic | 0.243 | Stabilizing | 0.506 | D | 0.313 | neutral | None | None | None | None | N |
| N/S | 0.0933 | likely_benign | 0.0831 | benign | -0.249 | Destabilizing | 0.002 | N | 0.196 | neutral | N | 0.461519159 | None | None | N |
| N/T | 0.1861 | likely_benign | 0.1391 | benign | -0.105 | Destabilizing | 0.003 | N | 0.222 | neutral | N | 0.462540666 | None | None | N |
| N/V | 0.4554 | ambiguous | 0.375 | ambiguous | -0.299 | Destabilizing | 0.101 | N | 0.419 | neutral | None | None | None | None | N |
| N/W | 0.9647 | likely_pathogenic | 0.9381 | pathogenic | -0.797 | Destabilizing | 0.994 | D | 0.576 | neutral | None | None | None | None | N |
| N/Y | 0.5085 | ambiguous | 0.4094 | ambiguous | -0.554 | Destabilizing | 0.844 | D | 0.434 | neutral | N | 0.499708888 | 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.