Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33738 | 101437;101438;101439 | chr2:178535403;178535402;178535401 | chr2:179400130;179400129;179400128 |
| N2AB | 32097 | 96514;96515;96516 | chr2:178535403;178535402;178535401 | chr2:179400130;179400129;179400128 |
| N2A | 31170 | 93733;93734;93735 | chr2:178535403;178535402;178535401 | chr2:179400130;179400129;179400128 |
| N2B | 24673 | 74242;74243;74244 | chr2:178535403;178535402;178535401 | chr2:179400130;179400129;179400128 |
| Novex-1 | 24798 | 74617;74618;74619 | chr2:178535403;178535402;178535401 | chr2:179400130;179400129;179400128 |
| Novex-2 | 24865 | 74818;74819;74820 | chr2:178535403;178535402;178535401 | chr2:179400130;179400129;179400128 |
| 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 | rs56273463  |
-0.495 | 1.0 | N | 0.746 | 0.458 | None | gnomAD-2.1.1 | 5.62195E-03 | None | None | None | None | N | None | 1.44664E-03 | 4.04457E-03 | None | 4.34783E-03 | 0 | None | 2.51617E-03 | None | 4.2E-03 | 8.65875E-03 | 8.56742E-03 |
| R/C | rs56273463 |
-0.495 | 1.0 | N | 0.746 | 0.458 | None | gnomAD-3.1.2 | 5.99495E-03 | None | None | None | None | N | None | 1.54515E-03 | 5.37001E-03 | 0 | 2.59366E-03 | 0 | None | 5.09626E-03 | 0 | 1.00106E-02 | 2.27932E-03 | 5.2531E-03 |
| R/C | rs56273463 |
-0.495 | 1.0 | N | 0.746 | 0.458 | None | 1000 genomes | 2.79553E-03 | None | None | None | None | N | None | 0 | 1.15E-02 | None | None | 0 | 5E-03 | None | None | None | 1E-03 | None |
| R/C | rs56273463 |
-0.495 | 1.0 | N | 0.746 | 0.458 | None | gnomAD-4.0.0 | 8.66767E-03 | None | None | None | None | N | None | 1.63969E-03 | 4.61574E-03 | None | 3.91865E-03 | 2.22826E-05 | None | 4.95746E-03 | 8.2481E-04 | 1.0505E-02 | 2.60211E-03 | 8.28986E-03 |
| R/H | rs192391568 |
-1.225 | 1.0 | N | 0.771 | 0.382 | None | gnomAD-2.1.1 | 1.14138E-04 | None | None | None | None | N | None | 1.23987E-04 | 1.41427E-04 | None | 0 | 5.12E-05 | None | 5.55556E-04 | None | 0 | 3.9E-05 | 1.40252E-04 |
| R/H | rs192391568 |
-1.225 | 1.0 | N | 0.771 | 0.382 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 1.20598E-04 | 1.3089E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 2.07039E-04 | 0 |
| R/H | rs192391568 |
-1.225 | 1.0 | N | 0.771 | 0.382 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/H | rs192391568 |
-1.225 | 1.0 | N | 0.771 | 0.382 | None | gnomAD-4.0.0 | 5.63842E-05 | None | None | None | None | N | None | 1.0659E-04 | 1.16624E-04 | None | 0 | 2.22806E-05 | None | 0 | 4.94886E-04 | 1.69515E-05 | 5.16007E-04 | 8.00179E-05 |
| R/S | None | None | 1.0 | N | 0.75 | 0.411 | 0.42526943336 | gnomAD-4.0.0 | 6.84197E-07 | None | None | None | None | N | None | 2.98757E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9277 | likely_pathogenic | 0.874 | pathogenic | -0.228 | Destabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | N |
| R/C | 0.733 | likely_pathogenic | 0.6033 | pathogenic | -0.331 | Destabilizing | 1.0 | D | 0.746 | deleterious | N | 0.474446658 | None | None | N |
| R/D | 0.9813 | likely_pathogenic | 0.971 | pathogenic | -0.005 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| R/E | 0.9078 | likely_pathogenic | 0.8549 | pathogenic | 0.106 | Stabilizing | 0.997 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/F | 0.9652 | likely_pathogenic | 0.9467 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | N |
| R/G | 0.9167 | likely_pathogenic | 0.8741 | pathogenic | -0.505 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.473686189 | None | None | N |
| R/H | 0.4966 | ambiguous | 0.4067 | ambiguous | -0.934 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.494140505 | None | None | N |
| R/I | 0.8811 | likely_pathogenic | 0.7728 | pathogenic | 0.496 | Stabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| R/K | 0.3814 | ambiguous | 0.3142 | benign | -0.317 | Destabilizing | 0.979 | D | 0.535 | neutral | None | None | None | None | N |
| R/L | 0.7773 | likely_pathogenic | 0.646 | pathogenic | 0.496 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.482579504 | None | None | N |
| R/M | 0.8987 | likely_pathogenic | 0.8227 | pathogenic | -0.024 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| R/N | 0.9671 | likely_pathogenic | 0.9486 | pathogenic | -0.008 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| R/P | 0.9091 | likely_pathogenic | 0.8317 | pathogenic | 0.277 | Stabilizing | 1.0 | D | 0.75 | deleterious | N | 0.454854185 | None | None | N |
| R/Q | 0.4334 | ambiguous | 0.3314 | benign | -0.082 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/S | 0.9595 | likely_pathogenic | 0.93 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.75 | deleterious | N | 0.47636282 | None | None | N |
| R/T | 0.8954 | likely_pathogenic | 0.8077 | pathogenic | -0.232 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| R/V | 0.881 | likely_pathogenic | 0.7884 | pathogenic | 0.277 | Stabilizing | 0.999 | D | 0.77 | deleterious | None | None | None | None | N |
| R/W | 0.7454 | likely_pathogenic | 0.6767 | pathogenic | -0.034 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| R/Y | 0.9237 | likely_pathogenic | 0.8848 | pathogenic | 0.314 | Stabilizing | 0.999 | D | 0.755 | deleterious | 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.