Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25844 | 77755;77756;77757 | chr2:178568602;178568601;178568600 | chr2:179433329;179433328;179433327 |
| N2AB | 24203 | 72832;72833;72834 | chr2:178568602;178568601;178568600 | chr2:179433329;179433328;179433327 |
| N2A | 23276 | 70051;70052;70053 | chr2:178568602;178568601;178568600 | chr2:179433329;179433328;179433327 |
| N2B | 16779 | 50560;50561;50562 | chr2:178568602;178568601;178568600 | chr2:179433329;179433328;179433327 |
| Novex-1 | 16904 | 50935;50936;50937 | chr2:178568602;178568601;178568600 | chr2:179433329;179433328;179433327 |
| Novex-2 | 16971 | 51136;51137;51138 | chr2:178568602;178568601;178568600 | chr2:179433329;179433328;179433327 |
| 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/F | rs1216073181  |
None | None | N | 0.218 | 0.256 | 0.187945064343 | gnomAD-4.0.0 | 1.59197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85977E-06 | 0 | 0 |
| I/V | rs1216073181 |
-1.611 | None | N | 0.115 | 0.217 | 0.203808441222 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66389E-04 |
| I/V | rs1216073181 |
-1.611 | None | N | 0.115 | 0.217 | 0.203808441222 | gnomAD-4.0.0 | 1.59197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02535E-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 | 0.6176 | likely_pathogenic | 0.5725 | pathogenic | -2.55 | Highly Destabilizing | 0.007 | N | 0.363 | neutral | None | None | None | None | N |
| I/C | 0.6647 | likely_pathogenic | 0.644 | pathogenic | -2.149 | Highly Destabilizing | 0.356 | N | 0.553 | neutral | None | None | None | None | N |
| I/D | 0.9429 | likely_pathogenic | 0.9364 | pathogenic | -2.589 | Highly Destabilizing | 0.356 | N | 0.61 | neutral | None | None | None | None | N |
| I/E | 0.8422 | likely_pathogenic | 0.83 | pathogenic | -2.475 | Highly Destabilizing | 0.136 | N | 0.587 | neutral | None | None | None | None | N |
| I/F | 0.2674 | likely_benign | 0.2601 | benign | -1.757 | Destabilizing | None | N | 0.218 | neutral | N | 0.457425635 | None | None | N |
| I/G | 0.8411 | likely_pathogenic | 0.8198 | pathogenic | -3.003 | Highly Destabilizing | 0.136 | N | 0.583 | neutral | None | None | None | None | N |
| I/H | 0.7967 | likely_pathogenic | 0.7781 | pathogenic | -2.24 | Highly Destabilizing | 0.864 | D | 0.569 | neutral | None | None | None | None | N |
| I/K | 0.7312 | likely_pathogenic | 0.7226 | pathogenic | -1.991 | Destabilizing | 0.136 | N | 0.588 | neutral | None | None | None | None | N |
| I/L | 0.1154 | likely_benign | 0.1056 | benign | -1.295 | Destabilizing | None | N | 0.111 | neutral | N | 0.425198573 | None | None | N |
| I/M | 0.1067 | likely_benign | 0.1039 | benign | -1.248 | Destabilizing | 0.171 | N | 0.547 | neutral | N | 0.478283697 | None | None | N |
| I/N | 0.5854 | likely_pathogenic | 0.551 | ambiguous | -2.085 | Highly Destabilizing | 0.56 | D | 0.588 | neutral | N | 0.486937459 | None | None | N |
| I/P | 0.9882 | likely_pathogenic | 0.9892 | pathogenic | -1.689 | Destabilizing | 0.356 | N | 0.601 | neutral | None | None | None | None | N |
| I/Q | 0.7202 | likely_pathogenic | 0.7063 | pathogenic | -2.154 | Highly Destabilizing | 0.628 | D | 0.59 | neutral | None | None | None | None | N |
| I/R | 0.6887 | likely_pathogenic | 0.6773 | pathogenic | -1.445 | Destabilizing | 0.356 | N | 0.587 | neutral | None | None | None | None | N |
| I/S | 0.5939 | likely_pathogenic | 0.5534 | ambiguous | -2.804 | Highly Destabilizing | 0.055 | N | 0.528 | neutral | N | 0.501083199 | None | None | N |
| I/T | 0.3777 | ambiguous | 0.3214 | benign | -2.554 | Highly Destabilizing | 0.012 | N | 0.465 | neutral | N | 0.478918415 | None | None | N |
| I/V | 0.0696 | likely_benign | 0.0648 | benign | -1.689 | Destabilizing | None | N | 0.115 | neutral | N | 0.370902729 | None | None | N |
| I/W | 0.8813 | likely_pathogenic | 0.8749 | pathogenic | -1.95 | Destabilizing | 0.864 | D | 0.573 | neutral | None | None | None | None | N |
| I/Y | 0.6758 | likely_pathogenic | 0.676 | pathogenic | -1.728 | Destabilizing | 0.038 | N | 0.548 | 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.