Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28794 | 86605;86606;86607 | chr2:178559752;178559751;178559750 | chr2:179424479;179424478;179424477 |
| N2AB | 27153 | 81682;81683;81684 | chr2:178559752;178559751;178559750 | chr2:179424479;179424478;179424477 |
| N2A | 26226 | 78901;78902;78903 | chr2:178559752;178559751;178559750 | chr2:179424479;179424478;179424477 |
| N2B | 19729 | 59410;59411;59412 | chr2:178559752;178559751;178559750 | chr2:179424479;179424478;179424477 |
| Novex-1 | 19854 | 59785;59786;59787 | chr2:178559752;178559751;178559750 | chr2:179424479;179424478;179424477 |
| Novex-2 | 19921 | 59986;59987;59988 | chr2:178559752;178559751;178559750 | chr2:179424479;179424478;179424477 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.958 | N | 0.506 | 0.218 | 0.303453137403 | gnomAD-4.0.0 | 1.3824E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.81152E-06 | 0 | 0 |
| D/H | None | None | 0.998 | N | 0.704 | 0.451 | 0.40032279838 | gnomAD-4.0.0 | 1.63125E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.92543E-06 | 0 | 0 |
| D/V | rs544440335  |
0.569 | 0.994 | N | 0.701 | 0.543 | 0.612322911341 | gnomAD-2.1.1 | 4.23E-06 | None | None | None | None | N | None | 6.51E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs544440335 |
0.569 | 0.994 | N | 0.701 | 0.543 | 0.612322911341 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs544440335 |
0.569 | 0.994 | N | 0.701 | 0.543 | 0.612322911341 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/V | rs544440335 |
0.569 | 0.994 | N | 0.701 | 0.543 | 0.612322911341 | gnomAD-4.0.0 | 6.56978E-06 | None | None | None | None | N | None | 2.40639E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2992 | likely_benign | 0.3166 | benign | -0.109 | Destabilizing | 0.988 | D | 0.627 | neutral | N | 0.50229392 | None | None | N |
| D/C | 0.7367 | likely_pathogenic | 0.7383 | pathogenic | 0.124 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/E | 0.2756 | likely_benign | 0.2734 | benign | -0.174 | Destabilizing | 0.958 | D | 0.506 | neutral | N | 0.455116049 | None | None | N |
| D/F | 0.7614 | likely_pathogenic | 0.7776 | pathogenic | -0.125 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| D/G | 0.4328 | ambiguous | 0.456 | ambiguous | -0.273 | Destabilizing | 0.919 | D | 0.681 | prob.neutral | N | 0.493089524 | None | None | N |
| D/H | 0.4862 | ambiguous | 0.5162 | ambiguous | 0.16 | Stabilizing | 0.998 | D | 0.704 | prob.neutral | N | 0.484442243 | None | None | N |
| D/I | 0.4821 | ambiguous | 0.4906 | ambiguous | 0.262 | Stabilizing | 0.995 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/K | 0.685 | likely_pathogenic | 0.7051 | pathogenic | 0.525 | Stabilizing | 0.991 | D | 0.694 | prob.neutral | None | None | None | None | N |
| D/L | 0.5564 | ambiguous | 0.5777 | pathogenic | 0.262 | Stabilizing | 0.995 | D | 0.702 | prob.neutral | None | None | None | None | N |
| D/M | 0.7313 | likely_pathogenic | 0.7395 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| D/N | 0.1333 | likely_benign | 0.137 | benign | 0.234 | Stabilizing | 0.142 | N | 0.379 | neutral | N | 0.495175947 | None | None | N |
| D/P | 0.6743 | likely_pathogenic | 0.7117 | pathogenic | 0.16 | Stabilizing | 0.998 | D | 0.718 | prob.delet. | None | None | None | None | N |
| D/Q | 0.5779 | likely_pathogenic | 0.5908 | pathogenic | 0.262 | Stabilizing | 0.991 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/R | 0.6995 | likely_pathogenic | 0.7204 | pathogenic | 0.653 | Stabilizing | 0.991 | D | 0.681 | prob.neutral | None | None | None | None | N |
| D/S | 0.2166 | likely_benign | 0.2279 | benign | 0.146 | Stabilizing | 0.938 | D | 0.654 | neutral | None | None | None | None | N |
| D/T | 0.4294 | ambiguous | 0.4428 | ambiguous | 0.277 | Stabilizing | 0.991 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/V | 0.2921 | likely_benign | 0.3014 | benign | 0.16 | Stabilizing | 0.994 | D | 0.701 | prob.neutral | N | 0.504603506 | None | None | N |
| D/W | 0.9523 | likely_pathogenic | 0.9574 | pathogenic | -0.039 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/Y | 0.3725 | ambiguous | 0.3889 | ambiguous | 0.109 | Stabilizing | 0.999 | D | 0.693 | prob.neutral | N | 0.500344452 | 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.