Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16339 | 49240;49241;49242 | chr2:178614499;178614498;178614497 | chr2:179479226;179479225;179479224 |
| N2AB | 14698 | 44317;44318;44319 | chr2:178614499;178614498;178614497 | chr2:179479226;179479225;179479224 |
| N2A | 13771 | 41536;41537;41538 | chr2:178614499;178614498;178614497 | chr2:179479226;179479225;179479224 |
| N2B | 7274 | 22045;22046;22047 | chr2:178614499;178614498;178614497 | chr2:179479226;179479225;179479224 |
| Novex-1 | 7399 | 22420;22421;22422 | chr2:178614499;178614498;178614497 | chr2:179479226;179479225;179479224 |
| Novex-2 | 7466 | 22621;22622;22623 | chr2:178614499;178614498;178614497 | chr2:179479226;179479225;179479224 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs558487304  |
0.019 | 1.0 | N | 0.731 | 0.379 | 0.351614576976 | gnomAD-2.1.1 | 2.03E-05 | None | None | None | None | I | None | 0 | 1.16734E-04 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| R/Q | rs558487304 |
0.019 | 1.0 | N | 0.731 | 0.379 | 0.351614576976 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs558487304 |
0.019 | 1.0 | N | 0.731 | 0.379 | 0.351614576976 | gnomAD-4.0.0 | 1.6769E-05 | None | None | None | None | I | None | 2.67609E-05 | 1.00388E-04 | None | 0 | 0 | None | 0 | 0 | 1.35837E-05 | 2.20897E-05 | 1.60524E-05 |
| R/W | rs201793958 |
-0.399 | 1.0 | D | 0.739 | 0.527 | None | gnomAD-2.1.1 | 1.00704E-04 | None | None | None | None | I | None | 9.52223E-04 | 2.85E-05 | None | 0 | 5.21E-05 | None | 0 | None | 0 | 2.36E-05 | 0 |
| R/W | rs201793958 |
-0.399 | 1.0 | D | 0.739 | 0.527 | None | gnomAD-3.1.2 | 2.96638E-04 | None | None | None | None | I | None | 8.95233E-04 | 1.97109E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 4.79846E-04 |
| R/W | rs201793958 |
-0.399 | 1.0 | D | 0.739 | 0.527 | None | gnomAD-4.0.0 | 5.34041E-05 | None | None | None | None | I | None | 8.83581E-04 | 8.36176E-05 | None | 0 | 0 | None | 0 | 1.64908E-04 | 8.48876E-06 | 0 | 6.41972E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8727 | likely_pathogenic | 0.8854 | pathogenic | None | Stabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | I |
| R/C | 0.5401 | ambiguous | 0.5815 | pathogenic | -0.198 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| R/D | 0.9551 | likely_pathogenic | 0.9558 | pathogenic | -0.167 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| R/E | 0.7499 | likely_pathogenic | 0.7715 | pathogenic | -0.114 | Destabilizing | 0.999 | D | 0.692 | prob.neutral | None | None | None | None | I |
| R/F | 0.9186 | likely_pathogenic | 0.9266 | pathogenic | -0.249 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/G | 0.8238 | likely_pathogenic | 0.8395 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.637 | neutral | D | 0.538385742 | None | None | I |
| R/H | 0.2507 | likely_benign | 0.2685 | benign | -0.63 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | I |
| R/I | 0.7416 | likely_pathogenic | 0.7698 | pathogenic | 0.419 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| R/K | 0.1974 | likely_benign | 0.2047 | benign | -0.112 | Destabilizing | 0.998 | D | 0.515 | neutral | None | None | None | None | I |
| R/L | 0.7167 | likely_pathogenic | 0.7473 | pathogenic | 0.419 | Stabilizing | 1.0 | D | 0.637 | neutral | D | 0.530215558 | None | None | I |
| R/M | 0.7327 | likely_pathogenic | 0.7616 | pathogenic | -0.001 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| R/N | 0.8906 | likely_pathogenic | 0.8999 | pathogenic | 0.079 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| R/P | 0.983 | likely_pathogenic | 0.9823 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | N | 0.512211534 | None | None | I |
| R/Q | 0.2577 | likely_benign | 0.2857 | benign | -0.014 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.496188431 | None | None | I |
| R/S | 0.8734 | likely_pathogenic | 0.8864 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/T | 0.6655 | likely_pathogenic | 0.6849 | pathogenic | -0.044 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| R/V | 0.7853 | likely_pathogenic | 0.8046 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| R/W | 0.615 | likely_pathogenic | 0.648 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.646308856 | None | None | I |
| R/Y | 0.8361 | likely_pathogenic | 0.8517 | pathogenic | 0.069 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
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.