Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29499 | 88720;88721;88722 | chr2:178554964;178554963;178554962 | chr2:179419691;179419690;179419689 |
| N2AB | 27858 | 83797;83798;83799 | chr2:178554964;178554963;178554962 | chr2:179419691;179419690;179419689 |
| N2A | 26931 | 81016;81017;81018 | chr2:178554964;178554963;178554962 | chr2:179419691;179419690;179419689 |
| N2B | 20434 | 61525;61526;61527 | chr2:178554964;178554963;178554962 | chr2:179419691;179419690;179419689 |
| Novex-1 | 20559 | 61900;61901;61902 | chr2:178554964;178554963;178554962 | chr2:179419691;179419690;179419689 |
| Novex-2 | 20626 | 62101;62102;62103 | chr2:178554964;178554963;178554962 | chr2:179419691;179419690;179419689 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs968816753  |
None | 0.007 | N | 0.299 | 0.142 | 0.422762650823 | gnomAD-4.0.0 | 1.59147E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85804E-06 | 0 | 0 |
| L/R | rs72648234 |
-0.882 | 0.939 | N | 0.564 | 0.433 | None | gnomAD-2.1.1 | 1.42956E-04 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.04983E-04 | 0 |
| L/R | rs72648234 |
-0.882 | 0.939 | N | 0.564 | 0.433 | None | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.76382E-04 | 0 | 0 |
| L/R | rs72648234 |
-0.882 | 0.939 | N | 0.564 | 0.433 | None | gnomAD-4.0.0 | 1.56789E-04 | None | None | None | None | N | None | 4.00481E-05 | 0 | None | 0 | 0 | None | 1.56294E-05 | 0 | 2.0342E-04 | 0 | 1.44125E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1712 | likely_benign | 0.1755 | benign | -2.114 | Highly Destabilizing | 0.373 | N | 0.503 | neutral | None | None | None | None | N |
| L/C | 0.3133 | likely_benign | 0.3092 | benign | -1.522 | Destabilizing | 0.996 | D | 0.533 | neutral | None | None | None | None | N |
| L/D | 0.535 | ambiguous | 0.515 | ambiguous | -1.721 | Destabilizing | 0.91 | D | 0.591 | neutral | None | None | None | None | N |
| L/E | 0.2767 | likely_benign | 0.26 | benign | -1.662 | Destabilizing | 0.91 | D | 0.579 | neutral | None | None | None | None | N |
| L/F | 0.0858 | likely_benign | 0.085 | benign | -1.379 | Destabilizing | 0.007 | N | 0.299 | neutral | N | 0.430836466 | None | None | N |
| L/G | 0.5097 | ambiguous | 0.502 | ambiguous | -2.496 | Highly Destabilizing | 0.742 | D | 0.564 | neutral | None | None | None | None | N |
| L/H | 0.1146 | likely_benign | 0.1163 | benign | -1.609 | Destabilizing | 0.994 | D | 0.592 | neutral | N | 0.487383183 | None | None | N |
| L/I | 0.0644 | likely_benign | 0.0667 | benign | -1.095 | Destabilizing | 0.007 | N | 0.391 | neutral | N | 0.429969675 | None | None | N |
| L/K | 0.2578 | likely_benign | 0.2412 | benign | -1.483 | Destabilizing | 0.91 | D | 0.561 | neutral | None | None | None | None | N |
| L/M | 0.085 | likely_benign | 0.0873 | benign | -0.989 | Destabilizing | 0.91 | D | 0.543 | neutral | None | None | None | None | N |
| L/N | 0.2504 | likely_benign | 0.2589 | benign | -1.405 | Destabilizing | 0.91 | D | 0.592 | neutral | None | None | None | None | N |
| L/P | 0.9459 | likely_pathogenic | 0.9282 | pathogenic | -1.407 | Destabilizing | 0.939 | D | 0.588 | neutral | N | 0.517186015 | None | None | N |
| L/Q | 0.1066 | likely_benign | 0.1088 | benign | -1.552 | Destabilizing | 0.953 | D | 0.562 | neutral | None | None | None | None | N |
| L/R | 0.1698 | likely_benign | 0.1564 | benign | -0.903 | Destabilizing | 0.939 | D | 0.564 | neutral | N | 0.431180396 | None | None | N |
| L/S | 0.1672 | likely_benign | 0.1683 | benign | -2.111 | Highly Destabilizing | 0.101 | N | 0.455 | neutral | None | None | None | None | N |
| L/T | 0.1097 | likely_benign | 0.1139 | benign | -1.933 | Destabilizing | 0.59 | D | 0.48 | neutral | None | None | None | None | N |
| L/V | 0.0662 | likely_benign | 0.0677 | benign | -1.407 | Destabilizing | 0.134 | N | 0.551 | neutral | N | 0.416944449 | None | None | N |
| L/W | 0.1896 | likely_benign | 0.1815 | benign | -1.462 | Destabilizing | 0.996 | D | 0.569 | neutral | None | None | None | None | N |
| L/Y | 0.2338 | likely_benign | 0.2252 | benign | -1.257 | Destabilizing | 0.835 | D | 0.539 | neutral | 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.