Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27859 | 83800;83801;83802 | chr2:178562557;178562556;178562555 | chr2:179427284;179427283;179427282 |
| N2AB | 26218 | 78877;78878;78879 | chr2:178562557;178562556;178562555 | chr2:179427284;179427283;179427282 |
| N2A | 25291 | 76096;76097;76098 | chr2:178562557;178562556;178562555 | chr2:179427284;179427283;179427282 |
| N2B | 18794 | 56605;56606;56607 | chr2:178562557;178562556;178562555 | chr2:179427284;179427283;179427282 |
| Novex-1 | 18919 | 56980;56981;56982 | chr2:178562557;178562556;178562555 | chr2:179427284;179427283;179427282 |
| Novex-2 | 18986 | 57181;57182;57183 | chr2:178562557;178562556;178562555 | chr2:179427284;179427283;179427282 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs761633407  |
0.841 | 0.981 | N | 0.668 | 0.259 | 0.31501682445 | gnomAD-2.1.1 | 7.32E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 9.53556E-04 | None | 3.37E-05 | None | 0 | 0 | 0 |
| K/E | rs761633407 |
0.841 | 0.981 | N | 0.668 | 0.259 | 0.31501682445 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 9.64878E-04 | None | 0 | 0 | 0 | 0 | 0 |
| K/E | rs761633407 |
0.841 | 0.981 | N | 0.668 | 0.259 | 0.31501682445 | gnomAD-4.0.0 | 2.483E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.47264E-04 | None | 0 | 0 | 0 | 7.75297E-05 | 6.41293E-05 |
| K/N | None | None | 0.999 | N | 0.658 | 0.23 | 0.285698343383 | gnomAD-4.0.0 | 1.59889E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77747E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.7127 | likely_pathogenic | 0.7274 | pathogenic | -0.167 | Destabilizing | 0.998 | D | 0.664 | prob.neutral | None | None | None | None | N |
| K/C | 0.8254 | likely_pathogenic | 0.8219 | pathogenic | -0.377 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| K/D | 0.945 | likely_pathogenic | 0.9519 | pathogenic | 0.511 | Stabilizing | 0.999 | D | 0.733 | deleterious | None | None | None | None | N |
| K/E | 0.6511 | likely_pathogenic | 0.6939 | pathogenic | 0.546 | Stabilizing | 0.981 | D | 0.668 | prob.neutral | N | 0.501141048 | None | None | N |
| K/F | 0.9111 | likely_pathogenic | 0.9215 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| K/G | 0.8831 | likely_pathogenic | 0.8973 | pathogenic | -0.398 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | N |
| K/H | 0.5276 | ambiguous | 0.5317 | ambiguous | -0.664 | Destabilizing | 1.0 | D | 0.72 | deleterious | None | None | None | None | N |
| K/I | 0.5057 | ambiguous | 0.5179 | ambiguous | 0.37 | Stabilizing | 0.991 | D | 0.773 | deleterious | N | 0.511568685 | None | None | N |
| K/L | 0.5113 | ambiguous | 0.5409 | ambiguous | 0.37 | Stabilizing | 0.979 | D | 0.593 | neutral | None | None | None | None | N |
| K/M | 0.3911 | ambiguous | 0.429 | ambiguous | 0.192 | Stabilizing | 1.0 | D | 0.732 | deleterious | None | None | None | None | N |
| K/N | 0.8371 | likely_pathogenic | 0.8541 | pathogenic | 0.167 | Stabilizing | 0.999 | D | 0.658 | prob.neutral | N | 0.480693493 | None | None | N |
| K/P | 0.9017 | likely_pathogenic | 0.9062 | pathogenic | 0.22 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| K/Q | 0.3147 | likely_benign | 0.3308 | benign | 0.018 | Stabilizing | 0.986 | D | 0.685 | prob.delet. | N | 0.515859784 | None | None | N |
| K/R | 0.0935 | likely_benign | 0.0911 | benign | -0.033 | Destabilizing | 0.185 | N | 0.399 | neutral | N | 0.498812819 | None | None | N |
| K/S | 0.8356 | likely_pathogenic | 0.854 | pathogenic | -0.487 | Destabilizing | 0.998 | D | 0.676 | prob.neutral | None | None | None | None | N |
| K/T | 0.4072 | ambiguous | 0.4114 | ambiguous | -0.28 | Destabilizing | 0.997 | D | 0.666 | prob.neutral | N | 0.463011442 | None | None | N |
| K/V | 0.4808 | ambiguous | 0.4914 | ambiguous | 0.22 | Stabilizing | 0.984 | D | 0.731 | deleterious | None | None | None | None | N |
| K/W | 0.8873 | likely_pathogenic | 0.9006 | pathogenic | -0.231 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| K/Y | 0.8345 | likely_pathogenic | 0.854 | pathogenic | 0.119 | Stabilizing | 0.996 | D | 0.764 | 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.