Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14819 | 44680;44681;44682 | chr2:178625366;178625365;178625364 | chr2:179490093;179490092;179490091 |
| N2AB | 13178 | 39757;39758;39759 | chr2:178625366;178625365;178625364 | chr2:179490093;179490092;179490091 |
| N2A | 12251 | 36976;36977;36978 | chr2:178625366;178625365;178625364 | chr2:179490093;179490092;179490091 |
| N2B | 5754 | 17485;17486;17487 | chr2:178625366;178625365;178625364 | chr2:179490093;179490092;179490091 |
| Novex-1 | 5879 | 17860;17861;17862 | chr2:178625366;178625365;178625364 | chr2:179490093;179490092;179490091 |
| Novex-2 | 5946 | 18061;18062;18063 | chr2:178625366;178625365;178625364 | chr2:179490093;179490092;179490091 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs778014249  |
0.352 | 0.901 | N | 0.663 | 0.446 | 0.563619085548 | gnomAD-2.1.1 | 8.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 6.142E-04 | 4.96E-05 | 0 |
| T/I | rs778014249 |
0.352 | 0.901 | N | 0.663 | 0.446 | 0.563619085548 | gnomAD-3.1.2 | 5.93E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 4.71609E-04 | 0 | 5.89E-05 | 0 | 0 |
| T/I | rs778014249 |
0.352 | 0.901 | N | 0.663 | 0.446 | 0.563619085548 | gnomAD-4.0.0 | 3.46377E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.88651E-04 | 1.66556E-04 | 1.87957E-05 | 0 | 1.62771E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1097 | likely_benign | 0.1178 | benign | -0.987 | Destabilizing | 0.003 | N | 0.302 | neutral | N | 0.520154996 | None | None | N |
| T/C | 0.413 | ambiguous | 0.4054 | ambiguous | -0.816 | Destabilizing | 0.989 | D | 0.682 | prob.neutral | None | None | None | None | N |
| T/D | 0.7279 | likely_pathogenic | 0.7955 | pathogenic | -1.833 | Destabilizing | 0.923 | D | 0.655 | neutral | None | None | None | None | N |
| T/E | 0.5019 | ambiguous | 0.5844 | pathogenic | -1.629 | Destabilizing | 0.775 | D | 0.643 | neutral | None | None | None | None | N |
| T/F | 0.238 | likely_benign | 0.2963 | benign | -0.675 | Destabilizing | 0.961 | D | 0.725 | prob.delet. | None | None | None | None | N |
| T/G | 0.3792 | ambiguous | 0.3702 | ambiguous | -1.401 | Destabilizing | 0.633 | D | 0.629 | neutral | None | None | None | None | N |
| T/H | 0.2526 | likely_benign | 0.3075 | benign | -1.671 | Destabilizing | 0.996 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/I | 0.1848 | likely_benign | 0.1651 | benign | 0.096 | Stabilizing | 0.901 | D | 0.663 | neutral | N | 0.520849663 | None | None | N |
| T/K | 0.2333 | likely_benign | 0.3289 | benign | -0.528 | Destabilizing | 0.722 | D | 0.649 | neutral | N | 0.498064924 | None | None | N |
| T/L | 0.1395 | likely_benign | 0.1823 | benign | 0.096 | Stabilizing | 0.633 | D | 0.607 | neutral | None | None | None | None | N |
| T/M | 0.1003 | likely_benign | 0.1252 | benign | 0.049 | Stabilizing | 0.996 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/N | 0.2342 | likely_benign | 0.2898 | benign | -1.312 | Destabilizing | 0.923 | D | 0.613 | neutral | None | None | None | None | N |
| T/P | 0.723 | likely_pathogenic | 0.8262 | pathogenic | -0.233 | Destabilizing | 0.949 | D | 0.687 | prob.neutral | D | 0.626182811 | None | None | N |
| T/Q | 0.2629 | likely_benign | 0.3095 | benign | -1.049 | Destabilizing | 0.961 | D | 0.702 | prob.neutral | None | None | None | None | N |
| T/R | 0.162 | likely_benign | 0.2347 | benign | -0.827 | Destabilizing | 0.901 | D | 0.699 | prob.neutral | N | 0.445587293 | None | None | N |
| T/S | 0.1309 | likely_benign | 0.1261 | benign | -1.417 | Destabilizing | 0.092 | N | 0.434 | neutral | N | 0.469728621 | None | None | N |
| T/V | 0.1554 | likely_benign | 0.1859 | benign | -0.233 | Destabilizing | 0.633 | D | 0.591 | neutral | None | None | None | None | N |
| T/W | 0.616 | likely_pathogenic | 0.6529 | pathogenic | -0.952 | Destabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/Y | 0.2771 | likely_benign | 0.3341 | benign | -0.52 | Destabilizing | 0.987 | D | 0.727 | prob.delet. | 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.