Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29541 | 88846;88847;88848 | chr2:178554726;178554725;178554724 | chr2:179419453;179419452;179419451 |
| N2AB | 27900 | 83923;83924;83925 | chr2:178554726;178554725;178554724 | chr2:179419453;179419452;179419451 |
| N2A | 26973 | 81142;81143;81144 | chr2:178554726;178554725;178554724 | chr2:179419453;179419452;179419451 |
| N2B | 20476 | 61651;61652;61653 | chr2:178554726;178554725;178554724 | chr2:179419453;179419452;179419451 |
| Novex-1 | 20601 | 62026;62027;62028 | chr2:178554726;178554725;178554724 | chr2:179419453;179419452;179419451 |
| Novex-2 | 20668 | 62227;62228;62229 | chr2:178554726;178554725;178554724 | chr2:179419453;179419452;179419451 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs768292510  |
-2.519 | 0.939 | N | 0.742 | 0.424 | 0.544825121038 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 5.12E-05 | None | 0 | None | 0 | 2.34E-05 | 1.40449E-04 |
| I/T | rs768292510 |
-2.519 | 0.939 | N | 0.742 | 0.424 | 0.544825121038 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs768292510 |
-2.519 | 0.939 | N | 0.742 | 0.424 | 0.544825121038 | gnomAD-4.0.0 | 3.34625E-05 | None | None | None | None | N | None | 6.67254E-05 | 1.66728E-05 | None | 3.37792E-05 | 6.6836E-05 | None | 0 | 1.64582E-04 | 3.22078E-05 | 1.09842E-05 | 6.40451E-05 |
| I/V | rs780639603 |
-1.172 | 0.02 | N | 0.207 | 0.088 | 0.222439326576 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.89E-06 | 0 |
| I/V | rs780639603 |
-1.172 | 0.02 | N | 0.207 | 0.088 | 0.222439326576 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 2.61952E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs780639603 |
-1.172 | 0.02 | N | 0.207 | 0.088 | 0.222439326576 | gnomAD-4.0.0 | 1.40892E-05 | None | None | None | None | N | None | 1.68725E-05 | 6.77713E-05 | None | 0 | 0 | None | 4.70662E-05 | 0 | 2.39284E-06 | 2.68183E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5671 | likely_pathogenic | 0.6099 | pathogenic | -2.295 | Highly Destabilizing | 0.91 | D | 0.654 | neutral | None | None | None | None | N |
| I/C | 0.8902 | likely_pathogenic | 0.9134 | pathogenic | -1.518 | Destabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| I/D | 0.9938 | likely_pathogenic | 0.9946 | pathogenic | -2.71 | Highly Destabilizing | 0.998 | D | 0.801 | deleterious | None | None | None | None | N |
| I/E | 0.9824 | likely_pathogenic | 0.9849 | pathogenic | -2.422 | Highly Destabilizing | 0.993 | D | 0.8 | deleterious | None | None | None | None | N |
| I/F | 0.4219 | ambiguous | 0.5009 | ambiguous | -1.215 | Destabilizing | 0.982 | D | 0.777 | deleterious | N | 0.514478491 | None | None | N |
| I/G | 0.9558 | likely_pathogenic | 0.9653 | pathogenic | -2.893 | Highly Destabilizing | 0.993 | D | 0.805 | deleterious | None | None | None | None | N |
| I/H | 0.9841 | likely_pathogenic | 0.9881 | pathogenic | -2.549 | Highly Destabilizing | 0.999 | D | 0.76 | deleterious | None | None | None | None | N |
| I/K | 0.9725 | likely_pathogenic | 0.9768 | pathogenic | -1.642 | Destabilizing | 0.993 | D | 0.798 | deleterious | None | None | None | None | N |
| I/L | 0.0907 | likely_benign | 0.1005 | benign | -0.538 | Destabilizing | 0.58 | D | 0.496 | neutral | N | 0.436430634 | None | None | N |
| I/M | 0.1267 | likely_benign | 0.1415 | benign | -0.649 | Destabilizing | 0.991 | D | 0.707 | prob.neutral | N | 0.515171925 | None | None | N |
| I/N | 0.9545 | likely_pathogenic | 0.9596 | pathogenic | -2.133 | Highly Destabilizing | 0.997 | D | 0.795 | deleterious | N | 0.499147505 | None | None | N |
| I/P | 0.8787 | likely_pathogenic | 0.9033 | pathogenic | -1.107 | Destabilizing | 0.998 | D | 0.794 | deleterious | None | None | None | None | N |
| I/Q | 0.9686 | likely_pathogenic | 0.9738 | pathogenic | -1.859 | Destabilizing | 0.998 | D | 0.794 | deleterious | None | None | None | None | N |
| I/R | 0.9586 | likely_pathogenic | 0.9667 | pathogenic | -1.653 | Destabilizing | 0.993 | D | 0.801 | deleterious | None | None | None | None | N |
| I/S | 0.8833 | likely_pathogenic | 0.8945 | pathogenic | -2.796 | Highly Destabilizing | 0.991 | D | 0.773 | deleterious | N | 0.48753771 | None | None | N |
| I/T | 0.6071 | likely_pathogenic | 0.6695 | pathogenic | -2.348 | Highly Destabilizing | 0.939 | D | 0.742 | deleterious | N | 0.521444536 | None | None | N |
| I/V | 0.0687 | likely_benign | 0.0739 | benign | -1.107 | Destabilizing | 0.02 | N | 0.207 | neutral | N | 0.434358695 | None | None | N |
| I/W | 0.974 | likely_pathogenic | 0.9829 | pathogenic | -1.665 | Destabilizing | 0.999 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9444 | likely_pathogenic | 0.9583 | pathogenic | -1.334 | Destabilizing | 0.993 | D | 0.721 | 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.