Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27889 | 83890;83891;83892 | chr2:178562467;178562466;178562465 | chr2:179427194;179427193;179427192 |
| N2AB | 26248 | 78967;78968;78969 | chr2:178562467;178562466;178562465 | chr2:179427194;179427193;179427192 |
| N2A | 25321 | 76186;76187;76188 | chr2:178562467;178562466;178562465 | chr2:179427194;179427193;179427192 |
| N2B | 18824 | 56695;56696;56697 | chr2:178562467;178562466;178562465 | chr2:179427194;179427193;179427192 |
| Novex-1 | 18949 | 57070;57071;57072 | chr2:178562467;178562466;178562465 | chr2:179427194;179427193;179427192 |
| Novex-2 | 19016 | 57271;57272;57273 | chr2:178562467;178562466;178562465 | chr2:179427194;179427193;179427192 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs1459332648  |
None | None | N | 0.079 | 0.067 | 0.143124449307 | 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 |
| S/N | rs1459332648 |
None | None | N | 0.079 | 0.067 | 0.143124449307 | gnomAD-4.0.0 | 2.5637E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.7878E-06 | 0 | 0 |
| S/R | rs779485837 |
-0.216 | None | N | 0.202 | 0.147 | 0.171388866994 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12108E-04 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1094 | likely_benign | 0.1089 | benign | -0.411 | Destabilizing | 0.031 | N | 0.334 | neutral | None | None | None | None | N |
| S/C | 0.0998 | likely_benign | 0.1061 | benign | -0.309 | Destabilizing | 0.828 | D | 0.405 | neutral | N | 0.494159147 | None | None | N |
| S/D | 0.4185 | ambiguous | 0.5346 | ambiguous | 0.072 | Stabilizing | 0.038 | N | 0.256 | neutral | None | None | None | None | N |
| S/E | 0.6155 | likely_pathogenic | 0.7079 | pathogenic | -0.004 | Destabilizing | 0.016 | N | 0.273 | neutral | None | None | None | None | N |
| S/F | 0.1931 | likely_benign | 0.1826 | benign | -0.903 | Destabilizing | 0.12 | N | 0.555 | neutral | None | None | None | None | N |
| S/G | 0.0944 | likely_benign | 0.1059 | benign | -0.559 | Destabilizing | 0.012 | N | 0.292 | neutral | N | 0.470204852 | None | None | N |
| S/H | 0.2081 | likely_benign | 0.2593 | benign | -1.055 | Destabilizing | None | N | 0.137 | neutral | None | None | None | None | N |
| S/I | 0.1774 | likely_benign | 0.2092 | benign | -0.149 | Destabilizing | 0.171 | N | 0.553 | neutral | N | 0.472455724 | None | None | N |
| S/K | 0.6808 | likely_pathogenic | 0.794 | pathogenic | -0.576 | Destabilizing | 0.016 | N | 0.265 | neutral | None | None | None | None | N |
| S/L | 0.1395 | likely_benign | 0.1329 | benign | -0.149 | Destabilizing | 0.038 | N | 0.48 | neutral | None | None | None | None | N |
| S/M | 0.1717 | likely_benign | 0.18 | benign | 0.078 | Stabilizing | 0.628 | D | 0.413 | neutral | None | None | None | None | N |
| S/N | 0.0923 | likely_benign | 0.1227 | benign | -0.333 | Destabilizing | None | N | 0.079 | neutral | N | 0.40640409 | None | None | N |
| S/P | 0.8633 | likely_pathogenic | 0.878 | pathogenic | -0.206 | Destabilizing | 0.356 | N | 0.469 | neutral | None | None | None | None | N |
| S/Q | 0.4913 | ambiguous | 0.5976 | pathogenic | -0.555 | Destabilizing | 0.072 | N | 0.353 | neutral | None | None | None | None | N |
| S/R | 0.6145 | likely_pathogenic | 0.7288 | pathogenic | -0.371 | Destabilizing | None | N | 0.202 | neutral | N | 0.447693352 | None | None | N |
| S/T | 0.089 | likely_benign | 0.0916 | benign | -0.411 | Destabilizing | 0.012 | N | 0.288 | neutral | N | 0.442479533 | None | None | N |
| S/V | 0.2043 | likely_benign | 0.2238 | benign | -0.206 | Destabilizing | 0.072 | N | 0.552 | neutral | None | None | None | None | N |
| S/W | 0.3035 | likely_benign | 0.2929 | benign | -0.909 | Destabilizing | 0.676 | D | 0.489 | neutral | None | None | None | None | N |
| S/Y | 0.1237 | likely_benign | 0.1276 | benign | -0.635 | Destabilizing | None | N | 0.279 | 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.