Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27702 | 83329;83330;83331 | chr2:178563028;178563027;178563026 | chr2:179427755;179427754;179427753 |
| N2AB | 26061 | 78406;78407;78408 | chr2:178563028;178563027;178563026 | chr2:179427755;179427754;179427753 |
| N2A | 25134 | 75625;75626;75627 | chr2:178563028;178563027;178563026 | chr2:179427755;179427754;179427753 |
| N2B | 18637 | 56134;56135;56136 | chr2:178563028;178563027;178563026 | chr2:179427755;179427754;179427753 |
| Novex-1 | 18762 | 56509;56510;56511 | chr2:178563028;178563027;178563026 | chr2:179427755;179427754;179427753 |
| Novex-2 | 18829 | 56710;56711;56712 | chr2:178563028;178563027;178563026 | chr2:179427755;179427754;179427753 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.996 | N | 0.561 | 0.418 | 0.619139198567 | gnomAD-4.0.0 | 1.36855E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31954E-05 | 0 |
| R/Q | rs776136653  |
-0.013 | 0.999 | N | 0.533 | 0.34 | 0.352048277211 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 1.15929E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65728E-04 |
| R/Q | rs776136653 |
-0.013 | 0.999 | N | 0.533 | 0.34 | 0.352048277211 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs776136653 |
-0.013 | 0.999 | N | 0.533 | 0.34 | 0.352048277211 | gnomAD-4.0.0 | 6.19771E-06 | None | None | None | None | N | None | 0 | 1.0005E-04 | None | 0 | 0 | None | 0 | 1.64582E-04 | 2.54301E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9204 | likely_pathogenic | 0.9201 | pathogenic | 0.092 | Stabilizing | 0.985 | D | 0.587 | neutral | None | None | None | None | N |
| R/C | 0.4022 | ambiguous | 0.4086 | ambiguous | -0.162 | Destabilizing | 1.0 | D | 0.633 | neutral | None | None | None | None | N |
| R/D | 0.9817 | likely_pathogenic | 0.9791 | pathogenic | -0.314 | Destabilizing | 0.998 | D | 0.539 | neutral | None | None | None | None | N |
| R/E | 0.8784 | likely_pathogenic | 0.8772 | pathogenic | -0.274 | Destabilizing | 0.985 | D | 0.555 | neutral | None | None | None | None | N |
| R/F | 0.8188 | likely_pathogenic | 0.7933 | pathogenic | -0.221 | Destabilizing | 0.999 | D | 0.583 | neutral | None | None | None | None | N |
| R/G | 0.896 | likely_pathogenic | 0.8915 | pathogenic | -0.045 | Destabilizing | 0.996 | D | 0.561 | neutral | D | 0.522003425 | None | None | N |
| R/H | 0.1958 | likely_benign | 0.1838 | benign | -0.572 | Destabilizing | 0.999 | D | 0.531 | neutral | None | None | None | None | N |
| R/I | 0.5907 | likely_pathogenic | 0.5644 | pathogenic | 0.407 | Stabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| R/K | 0.1929 | likely_benign | 0.2088 | benign | -0.097 | Destabilizing | 0.271 | N | 0.354 | neutral | None | None | None | None | N |
| R/L | 0.6619 | likely_pathogenic | 0.6457 | pathogenic | 0.407 | Stabilizing | 0.996 | D | 0.561 | neutral | N | 0.488415035 | None | None | N |
| R/M | 0.7213 | likely_pathogenic | 0.714 | pathogenic | -0.045 | Destabilizing | 1.0 | D | 0.542 | neutral | None | None | None | None | N |
| R/N | 0.9251 | likely_pathogenic | 0.9112 | pathogenic | 0.012 | Stabilizing | 0.998 | D | 0.528 | neutral | None | None | None | None | N |
| R/P | 0.994 | likely_pathogenic | 0.9947 | pathogenic | 0.32 | Stabilizing | 1.0 | D | 0.566 | neutral | D | 0.533777804 | None | None | N |
| R/Q | 0.2568 | likely_benign | 0.2646 | benign | -0.023 | Destabilizing | 0.999 | D | 0.533 | neutral | N | 0.492756674 | None | None | N |
| R/S | 0.9125 | likely_pathogenic | 0.9033 | pathogenic | -0.136 | Destabilizing | 0.985 | D | 0.614 | neutral | None | None | None | None | N |
| R/T | 0.8175 | likely_pathogenic | 0.7984 | pathogenic | 0.005 | Stabilizing | 0.993 | D | 0.561 | neutral | None | None | None | None | N |
| R/V | 0.7341 | likely_pathogenic | 0.7172 | pathogenic | 0.32 | Stabilizing | 0.998 | D | 0.565 | neutral | None | None | None | None | N |
| R/W | 0.4017 | ambiguous | 0.3917 | ambiguous | -0.42 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | N |
| R/Y | 0.6685 | likely_pathogenic | 0.6379 | pathogenic | -0.015 | Destabilizing | 0.999 | D | 0.575 | 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.