Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32257 | 96994;96995;96996 | chr2:178543204;178543203;178543202 | chr2:179407931;179407930;179407929 |
| N2AB | 30616 | 92071;92072;92073 | chr2:178543204;178543203;178543202 | chr2:179407931;179407930;179407929 |
| N2A | 29689 | 89290;89291;89292 | chr2:178543204;178543203;178543202 | chr2:179407931;179407930;179407929 |
| N2B | 23192 | 69799;69800;69801 | chr2:178543204;178543203;178543202 | chr2:179407931;179407930;179407929 |
| Novex-1 | 23317 | 70174;70175;70176 | chr2:178543204;178543203;178543202 | chr2:179407931;179407930;179407929 |
| Novex-2 | 23384 | 70375;70376;70377 | chr2:178543204;178543203;178543202 | chr2:179407931;179407930;179407929 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.92 | N | 0.395 | 0.323 | 0.491387584038 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| P/S | rs564715146  |
-0.943 | 0.31 | N | 0.169 | 0.172 | 0.191931220699 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/S | rs564715146 |
-0.943 | 0.31 | N | 0.169 | 0.172 | 0.191931220699 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07814E-04 | 0 |
| P/S | rs564715146 |
-0.943 | 0.31 | N | 0.169 | 0.172 | 0.191931220699 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| P/S | rs564715146 |
-0.943 | 0.31 | N | 0.169 | 0.172 | 0.191931220699 | gnomAD-4.0.0 | 3.84336E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.02134E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1135 | likely_benign | 0.1234 | benign | -1.173 | Destabilizing | 0.061 | N | 0.121 | neutral | N | 0.395805881 | None | None | I |
| P/C | 0.6092 | likely_pathogenic | 0.635 | pathogenic | -0.817 | Destabilizing | 0.999 | D | 0.381 | neutral | None | None | None | None | I |
| P/D | 0.6292 | likely_pathogenic | 0.6973 | pathogenic | -0.634 | Destabilizing | 0.939 | D | 0.369 | neutral | None | None | None | None | I |
| P/E | 0.5073 | ambiguous | 0.5665 | pathogenic | -0.616 | Destabilizing | 0.939 | D | 0.307 | neutral | None | None | None | None | I |
| P/F | 0.8046 | likely_pathogenic | 0.8203 | pathogenic | -0.774 | Destabilizing | 0.997 | D | 0.4 | neutral | None | None | None | None | I |
| P/G | 0.304 | likely_benign | 0.3572 | ambiguous | -1.504 | Destabilizing | 0.863 | D | 0.358 | neutral | None | None | None | None | I |
| P/H | 0.4043 | ambiguous | 0.4484 | ambiguous | -0.959 | Destabilizing | 0.999 | D | 0.364 | neutral | N | 0.521887253 | None | None | I |
| P/I | 0.5834 | likely_pathogenic | 0.6079 | pathogenic | -0.373 | Destabilizing | 0.982 | D | 0.404 | neutral | None | None | None | None | I |
| P/K | 0.5826 | likely_pathogenic | 0.6479 | pathogenic | -0.932 | Destabilizing | 0.939 | D | 0.317 | neutral | None | None | None | None | I |
| P/L | 0.2816 | likely_benign | 0.2729 | benign | -0.373 | Destabilizing | 0.92 | D | 0.395 | neutral | N | 0.460241362 | None | None | I |
| P/M | 0.524 | ambiguous | 0.5336 | ambiguous | -0.348 | Destabilizing | 0.999 | D | 0.364 | neutral | None | None | None | None | I |
| P/N | 0.4051 | ambiguous | 0.4612 | ambiguous | -0.776 | Destabilizing | 0.982 | D | 0.389 | neutral | None | None | None | None | I |
| P/Q | 0.32 | likely_benign | 0.3579 | ambiguous | -0.873 | Destabilizing | 0.991 | D | 0.386 | neutral | None | None | None | None | I |
| P/R | 0.4713 | ambiguous | 0.5275 | ambiguous | -0.499 | Destabilizing | 0.988 | D | 0.393 | neutral | N | 0.48475023 | None | None | I |
| P/S | 0.1492 | likely_benign | 0.1841 | benign | -1.364 | Destabilizing | 0.31 | N | 0.169 | neutral | N | 0.45443011 | None | None | I |
| P/T | 0.1575 | likely_benign | 0.1681 | benign | -1.222 | Destabilizing | 0.134 | N | 0.169 | neutral | N | 0.418549455 | None | None | I |
| P/V | 0.3703 | ambiguous | 0.3833 | ambiguous | -0.603 | Destabilizing | 0.939 | D | 0.363 | neutral | None | None | None | None | I |
| P/W | 0.8314 | likely_pathogenic | 0.8618 | pathogenic | -0.971 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | I |
| P/Y | 0.6651 | likely_pathogenic | 0.7054 | pathogenic | -0.654 | Destabilizing | 0.997 | D | 0.401 | neutral | None | None | None | None | I |
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.