Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29468 | 88627;88628;88629 | chr2:178555057;178555056;178555055 | chr2:179419784;179419783;179419782 |
| N2AB | 27827 | 83704;83705;83706 | chr2:178555057;178555056;178555055 | chr2:179419784;179419783;179419782 |
| N2A | 26900 | 80923;80924;80925 | chr2:178555057;178555056;178555055 | chr2:179419784;179419783;179419782 |
| N2B | 20403 | 61432;61433;61434 | chr2:178555057;178555056;178555055 | chr2:179419784;179419783;179419782 |
| Novex-1 | 20528 | 61807;61808;61809 | chr2:178555057;178555056;178555055 | chr2:179419784;179419783;179419782 |
| Novex-2 | 20595 | 62008;62009;62010 | chr2:178555057;178555056;178555055 | chr2:179419784;179419783;179419782 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs747441311  |
0.079 | 1.0 | D | 0.755 | 0.71 | 0.873541437591 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.67E-05 | 0 |
| P/L | rs747441311 |
0.079 | 1.0 | D | 0.755 | 0.71 | 0.873541437591 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07469E-04 | 0 |
| P/L | rs747441311 |
0.079 | 1.0 | D | 0.755 | 0.71 | 0.873541437591 | gnomAD-4.0.0 | 9.91551E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.62823E-06 | 5.49028E-05 | 3.20256E-05 |
| P/R | rs747441311 |
0.288 | 1.0 | D | 0.773 | 0.722 | 0.803054873015 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/R | rs747441311 |
0.288 | 1.0 | D | 0.773 | 0.722 | 0.803054873015 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/R | rs747441311 |
0.288 | 1.0 | D | 0.773 | 0.722 | 0.803054873015 | gnomAD-4.0.0 | 2.47888E-06 | None | None | None | None | I | None | 4.00534E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60128E-05 |
| P/S | rs769270365 |
-0.035 | 1.0 | D | 0.744 | 0.775 | 0.620317764101 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs769270365 |
-0.035 | 1.0 | D | 0.744 | 0.775 | 0.620317764101 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.9323 | likely_pathogenic | 0.901 | pathogenic | -0.419 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.521297361 | None | None | I |
| P/C | 0.9956 | likely_pathogenic | 0.9933 | pathogenic | -0.423 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | I |
| P/D | 0.985 | likely_pathogenic | 0.9787 | pathogenic | -0.52 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| P/E | 0.9813 | likely_pathogenic | 0.9726 | pathogenic | -0.653 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| P/F | 0.9964 | likely_pathogenic | 0.9934 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| P/G | 0.9825 | likely_pathogenic | 0.9751 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| P/H | 0.9826 | likely_pathogenic | 0.9738 | pathogenic | -0.217 | Destabilizing | 1.0 | D | 0.773 | deleterious | D | 0.596455564 | None | None | I |
| P/I | 0.9703 | likely_pathogenic | 0.9539 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| P/K | 0.9868 | likely_pathogenic | 0.9828 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| P/L | 0.9208 | likely_pathogenic | 0.8768 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.596455564 | None | None | I |
| P/M | 0.9786 | likely_pathogenic | 0.9665 | pathogenic | -0.269 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | I |
| P/N | 0.9867 | likely_pathogenic | 0.9813 | pathogenic | -0.055 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| P/Q | 0.979 | likely_pathogenic | 0.9697 | pathogenic | -0.345 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| P/R | 0.9735 | likely_pathogenic | 0.9656 | pathogenic | 0.113 | Stabilizing | 1.0 | D | 0.773 | deleterious | D | 0.596051956 | None | None | I |
| P/S | 0.9826 | likely_pathogenic | 0.9729 | pathogenic | -0.332 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.543667577 | None | None | I |
| P/T | 0.9385 | likely_pathogenic | 0.9124 | pathogenic | -0.377 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.580032595 | None | None | I |
| P/V | 0.9411 | likely_pathogenic | 0.9173 | pathogenic | -0.296 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| P/W | 0.9979 | likely_pathogenic | 0.9965 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| P/Y | 0.9931 | likely_pathogenic | 0.9893 | pathogenic | -0.574 | Destabilizing | 1.0 | D | 0.798 | deleterious | 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.