Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27694 | 83305;83306;83307 | chr2:178563052;178563051;178563050 | chr2:179427779;179427778;179427777 |
| N2AB | 26053 | 78382;78383;78384 | chr2:178563052;178563051;178563050 | chr2:179427779;179427778;179427777 |
| N2A | 25126 | 75601;75602;75603 | chr2:178563052;178563051;178563050 | chr2:179427779;179427778;179427777 |
| N2B | 18629 | 56110;56111;56112 | chr2:178563052;178563051;178563050 | chr2:179427779;179427778;179427777 |
| Novex-1 | 18754 | 56485;56486;56487 | chr2:178563052;178563051;178563050 | chr2:179427779;179427778;179427777 |
| Novex-2 | 18821 | 56686;56687;56688 | chr2:178563052;178563051;178563050 | chr2:179427779;179427778;179427777 |
| 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/C | rs192360370  |
-0.211 | 1.0 | N | 0.739 | 0.513 | None | gnomAD-2.1.1 | 3.03305E-04 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 3.9471E-03 | None | 0 | None | 0 | 3.9E-05 | 2.80505E-04 |
| R/C | rs192360370 |
-0.211 | 1.0 | N | 0.739 | 0.513 | None | gnomAD-3.1.2 | 1.2498E-04 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 3.48432E-03 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs192360370 |
-0.211 | 1.0 | N | 0.739 | 0.513 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 3E-03 | 0 | None | None | None | 0 | None |
| R/C | rs192360370 |
-0.211 | 1.0 | N | 0.739 | 0.513 | None | gnomAD-4.0.0 | 2.28682E-04 | None | None | None | None | I | None | 1.33369E-05 | 5.00117E-05 | None | 0 | 7.40311E-03 | None | 0 | 0 | 2.37353E-05 | 0 | 8.00307E-05 |
| R/H | rs775499341 |
-0.603 | 1.0 | N | 0.751 | 0.434 | 0.270001397563 | gnomAD-2.1.1 | 1.71307E-04 | None | None | None | None | I | None | 4.13E-05 | 2.83E-05 | None | 0 | 2.1017E-03 | None | 0 | None | 0 | 3.9E-05 | 0 |
| R/H | rs775499341 |
-0.603 | 1.0 | N | 0.751 | 0.434 | 0.270001397563 | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 9.68242E-04 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/H | rs775499341 |
-0.603 | 1.0 | N | 0.751 | 0.434 | 0.270001397563 | gnomAD-4.0.0 | 5.20616E-05 | None | None | None | None | I | None | 4.00695E-05 | 3.33578E-05 | None | 0 | 6.01953E-04 | None | 0 | 0 | 4.15362E-05 | 0 | 4.80369E-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 | 0.9914 | likely_pathogenic | 0.9892 | pathogenic | -0.315 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | I |
| R/C | 0.8231 | likely_pathogenic | 0.7935 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | N | 0.479494362 | None | None | I |
| R/D | 0.9952 | likely_pathogenic | 0.9938 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| R/E | 0.9673 | likely_pathogenic | 0.9584 | pathogenic | 0.146 | Stabilizing | 0.999 | D | 0.644 | neutral | None | None | None | None | I |
| R/F | 0.9888 | likely_pathogenic | 0.9871 | pathogenic | -0.291 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| R/G | 0.9804 | likely_pathogenic | 0.9744 | pathogenic | -0.588 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.502118067 | None | None | I |
| R/H | 0.484 | ambiguous | 0.3929 | ambiguous | -1.008 | Destabilizing | 1.0 | D | 0.751 | deleterious | N | 0.476669978 | None | None | I |
| R/I | 0.9695 | likely_pathogenic | 0.962 | pathogenic | 0.395 | Stabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| R/K | 0.6011 | likely_pathogenic | 0.58 | pathogenic | -0.307 | Destabilizing | 0.998 | D | 0.535 | neutral | None | None | None | None | I |
| R/L | 0.9418 | likely_pathogenic | 0.9329 | pathogenic | 0.395 | Stabilizing | 1.0 | D | 0.649 | neutral | N | 0.46675525 | None | None | I |
| R/M | 0.9721 | likely_pathogenic | 0.9641 | pathogenic | -0.092 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/N | 0.9842 | likely_pathogenic | 0.982 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| R/P | 0.9964 | likely_pathogenic | 0.9954 | pathogenic | 0.18 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | N | 0.513474373 | None | None | I |
| R/Q | 0.5754 | likely_pathogenic | 0.5499 | ambiguous | -0.107 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| R/S | 0.9849 | likely_pathogenic | 0.9809 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.461096937 | None | None | I |
| R/T | 0.9713 | likely_pathogenic | 0.962 | pathogenic | -0.293 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| R/V | 0.9742 | likely_pathogenic | 0.9689 | pathogenic | 0.18 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| R/W | 0.8175 | likely_pathogenic | 0.7859 | pathogenic | -0.152 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| R/Y | 0.95 | likely_pathogenic | 0.9413 | pathogenic | 0.204 | 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.