Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8363 | 25312;25313;25314 | chr2:178717787;178717786;178717785 | chr2:179582514;179582513;179582512 |
| N2AB | 8046 | 24361;24362;24363 | chr2:178717787;178717786;178717785 | chr2:179582514;179582513;179582512 |
| N2A | 7119 | 21580;21581;21582 | chr2:178717787;178717786;178717785 | chr2:179582514;179582513;179582512 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs778129279  |
-0.562 | 0.907 | N | 0.325 | 0.387 | 0.504052602331 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.14E-06 | 0 |
| A/E | rs778129279 |
-0.562 | 0.907 | N | 0.325 | 0.387 | 0.504052602331 | gnomAD-4.0.0 | 3.21451E-06 | None | None | None | None | N | None | 5.78972E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88361E-06 | 0 | 0 |
| A/G | rs778129279 |
-0.795 | 0.404 | N | 0.216 | 0.288 | 0.306695030598 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.66E-05 | None | 0 | None | 0 | 0 | 0 |
| A/G | rs778129279 |
-0.795 | 0.404 | N | 0.216 | 0.288 | 0.306695030598 | gnomAD-4.0.0 | 1.60726E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78009E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/P | rs200972189 |
-0.185 | 0.021 | N | 0.148 | 0.311 | None | gnomAD-2.1.1 | 1.1E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.4E-05 | 0 |
| A/P | rs200972189 |
-0.185 | 0.021 | N | 0.148 | 0.311 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/P | rs200972189 |
-0.185 | 0.021 | N | 0.148 | 0.311 | None | gnomAD-4.0.0 | 1.49324E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.66058E-04 | 1.95479E-05 | 0 | 0 |
| A/S | rs200972189 |
-0.77 | 0.02 | N | 0.127 | 0.221 | None | gnomAD-2.1.1 | 2.44767E-04 | None | None | None | None | N | None | 2.26036E-03 | 3.47162E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.44676E-04 |
| A/S | rs200972189 |
-0.77 | 0.02 | N | 0.127 | 0.221 | None | gnomAD-3.1.2 | 7.89038E-04 | None | None | None | None | N | None | 2.58342E-03 | 6.55136E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 9.56938E-04 |
| A/S | rs200972189 |
-0.77 | 0.02 | N | 0.127 | 0.221 | None | 1000 genomes | 9.98403E-04 | None | None | None | None | N | None | 3.8E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/S | rs200972189 |
-0.77 | 0.02 | N | 0.127 | 0.221 | None | gnomAD-4.0.0 | 1.41847E-04 | None | None | None | None | N | None | 2.45315E-03 | 4.0505E-04 | None | 0 | 0 | None | 0 | 0 | 2.54975E-06 | 0 | 2.8965E-04 |
| A/V | None | None | 0.116 | N | 0.14 | 0.251 | 0.346992582518 | gnomAD-4.0.0 | 1.60726E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88361E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6727 | likely_pathogenic | 0.7564 | pathogenic | -0.544 | Destabilizing | 0.999 | D | 0.301 | neutral | None | None | None | None | N |
| A/D | 0.4695 | ambiguous | 0.6719 | pathogenic | -0.812 | Destabilizing | 0.902 | D | 0.339 | neutral | None | None | None | None | N |
| A/E | 0.4067 | ambiguous | 0.5845 | pathogenic | -0.847 | Destabilizing | 0.907 | D | 0.325 | neutral | N | 0.469045351 | None | None | N |
| A/F | 0.443 | ambiguous | 0.6109 | pathogenic | -0.853 | Destabilizing | 0.996 | D | 0.355 | neutral | None | None | None | None | N |
| A/G | 0.176 | likely_benign | 0.2623 | benign | -0.984 | Destabilizing | 0.404 | N | 0.216 | neutral | N | 0.494024122 | None | None | N |
| A/H | 0.6015 | likely_pathogenic | 0.7252 | pathogenic | -1.031 | Destabilizing | 1.0 | D | 0.328 | neutral | None | None | None | None | N |
| A/I | 0.2822 | likely_benign | 0.4583 | ambiguous | -0.273 | Destabilizing | 0.945 | D | 0.324 | neutral | None | None | None | None | N |
| A/K | 0.6886 | likely_pathogenic | 0.8234 | pathogenic | -1.0 | Destabilizing | 0.972 | D | 0.325 | neutral | None | None | None | None | N |
| A/L | 0.2139 | likely_benign | 0.3243 | benign | -0.273 | Destabilizing | 0.877 | D | 0.277 | neutral | None | None | None | None | N |
| A/M | 0.3393 | likely_benign | 0.4996 | ambiguous | -0.205 | Destabilizing | 0.996 | D | 0.28 | neutral | None | None | None | None | N |
| A/N | 0.342 | ambiguous | 0.5005 | ambiguous | -0.672 | Destabilizing | 0.792 | D | 0.388 | neutral | None | None | None | None | N |
| A/P | 0.2573 | likely_benign | 0.3633 | ambiguous | -0.392 | Destabilizing | 0.021 | N | 0.148 | neutral | N | 0.488460618 | None | None | N |
| A/Q | 0.4355 | ambiguous | 0.5609 | ambiguous | -0.828 | Destabilizing | 0.996 | D | 0.326 | neutral | None | None | None | None | N |
| A/R | 0.5848 | likely_pathogenic | 0.7109 | pathogenic | -0.617 | Destabilizing | 0.992 | D | 0.327 | neutral | None | None | None | None | N |
| A/S | 0.0895 | likely_benign | 0.111 | benign | -1.009 | Destabilizing | 0.02 | N | 0.127 | neutral | N | 0.444725697 | None | None | N |
| A/T | 0.1042 | likely_benign | 0.1583 | benign | -0.954 | Destabilizing | 0.025 | N | 0.057 | neutral | N | 0.396702463 | None | None | N |
| A/V | 0.1446 | likely_benign | 0.242 | benign | -0.392 | Destabilizing | 0.116 | N | 0.14 | neutral | N | 0.451153024 | None | None | N |
| A/W | 0.8218 | likely_pathogenic | 0.9036 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.493 | neutral | None | None | None | None | N |
| A/Y | 0.5973 | likely_pathogenic | 0.7429 | pathogenic | -0.78 | Destabilizing | 0.999 | D | 0.347 | 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.