Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32071 | 96436;96437;96438 | chr2:178543933;178543932;178543931 | chr2:179408660;179408659;179408658 |
| N2AB | 30430 | 91513;91514;91515 | chr2:178543933;178543932;178543931 | chr2:179408660;179408659;179408658 |
| N2A | 29503 | 88732;88733;88734 | chr2:178543933;178543932;178543931 | chr2:179408660;179408659;179408658 |
| N2B | 23006 | 69241;69242;69243 | chr2:178543933;178543932;178543931 | chr2:179408660;179408659;179408658 |
| Novex-1 | 23131 | 69616;69617;69618 | chr2:178543933;178543932;178543931 | chr2:179408660;179408659;179408658 |
| Novex-2 | 23198 | 69817;69818;69819 | chr2:178543933;178543932;178543931 | chr2:179408660;179408659;179408658 |
| 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/R | rs755545981  |
-1.072 | 0.794 | N | 0.684 | 0.306 | 0.792153859373 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| I/R | rs755545981 |
-1.072 | 0.794 | N | 0.684 | 0.306 | 0.792153859373 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/R | rs755545981 |
-1.072 | 0.794 | N | 0.684 | 0.306 | 0.792153859373 | gnomAD-4.0.0 | 8.67651E-06 | None | None | None | None | N | None | 1.3359E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.10196E-05 | 0 | 0 |
| I/T | rs755545981 |
-2.261 | 0.003 | N | 0.398 | 0.159 | 0.520640030592 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/T | rs755545981 |
-2.261 | 0.003 | N | 0.398 | 0.159 | 0.520640030592 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 4.78011E-04 |
| I/T | rs755545981 |
-2.261 | 0.003 | N | 0.398 | 0.159 | 0.520640030592 | gnomAD-4.0.0 | 3.09853E-06 | None | None | None | None | N | None | 0 | 1.66694E-05 | None | 0 | 0 | None | 0 | 0 | 8.4767E-07 | 2.19597E-05 | 1.60067E-05 |
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 | 0.4173 | ambiguous | 0.4033 | ambiguous | -2.258 | Highly Destabilizing | 0.129 | N | 0.595 | neutral | None | None | None | None | N |
| I/C | 0.7782 | likely_pathogenic | 0.8016 | pathogenic | -1.521 | Destabilizing | 0.94 | D | 0.639 | neutral | None | None | None | None | N |
| I/D | 0.9199 | likely_pathogenic | 0.9144 | pathogenic | -2.04 | Highly Destabilizing | 0.836 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/E | 0.8133 | likely_pathogenic | 0.803 | pathogenic | -1.921 | Destabilizing | 0.593 | D | 0.699 | prob.neutral | None | None | None | None | N |
| I/F | 0.2645 | likely_benign | 0.2545 | benign | -1.349 | Destabilizing | 0.557 | D | 0.651 | neutral | None | None | None | None | N |
| I/G | 0.8452 | likely_pathogenic | 0.8365 | pathogenic | -2.707 | Highly Destabilizing | 0.593 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/H | 0.6863 | likely_pathogenic | 0.6747 | pathogenic | -1.968 | Destabilizing | 0.983 | D | 0.658 | neutral | None | None | None | None | N |
| I/K | 0.6808 | likely_pathogenic | 0.6637 | pathogenic | -1.743 | Destabilizing | 0.523 | D | 0.691 | prob.neutral | N | 0.491172849 | None | None | N |
| I/L | 0.1544 | likely_benign | 0.1405 | benign | -1.02 | Destabilizing | 0.001 | N | 0.19 | neutral | N | 0.484708237 | None | None | N |
| I/M | 0.1179 | likely_benign | 0.117 | benign | -0.89 | Destabilizing | 0.047 | N | 0.398 | neutral | N | 0.473280522 | None | None | N |
| I/N | 0.5275 | ambiguous | 0.503 | ambiguous | -1.761 | Destabilizing | 0.836 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/P | 0.9728 | likely_pathogenic | 0.9639 | pathogenic | -1.407 | Destabilizing | 0.94 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/Q | 0.6503 | likely_pathogenic | 0.6288 | pathogenic | -1.794 | Destabilizing | 0.836 | D | 0.68 | prob.neutral | None | None | None | None | N |
| I/R | 0.5543 | ambiguous | 0.5205 | ambiguous | -1.251 | Destabilizing | 0.794 | D | 0.684 | prob.neutral | N | 0.457116204 | None | None | N |
| I/S | 0.4295 | ambiguous | 0.4079 | ambiguous | -2.461 | Highly Destabilizing | 0.264 | N | 0.653 | neutral | None | None | None | None | N |
| I/T | 0.1626 | likely_benign | 0.1573 | benign | -2.218 | Highly Destabilizing | 0.003 | N | 0.398 | neutral | N | 0.408226179 | None | None | N |
| I/V | 0.0822 | likely_benign | 0.0877 | benign | -1.407 | Destabilizing | 0.001 | N | 0.187 | neutral | N | 0.397089252 | None | None | N |
| I/W | 0.838 | likely_pathogenic | 0.8335 | pathogenic | -1.578 | Destabilizing | 0.983 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/Y | 0.6627 | likely_pathogenic | 0.6619 | pathogenic | -1.343 | Destabilizing | 0.836 | D | 0.666 | 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.