Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7364 | 22315;22316;22317 | chr2:178722809;178722808;178722807 | chr2:179587536;179587535;179587534 |
| N2AB | 7047 | 21364;21365;21366 | chr2:178722809;178722808;178722807 | chr2:179587536;179587535;179587534 |
| N2A | 6120 | 18583;18584;18585 | chr2:178722809;178722808;178722807 | chr2:179587536;179587535;179587534 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/P | rs200128066  |
None | 1.0 | N | 0.561 | 0.393 | 0.53046153047 | gnomAD-4.0.0 | 6.8439E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9962E-07 | 0 | 0 |
| R/Q | rs200128066 |
0.153 | 1.0 | N | 0.507 | 0.269 | None | gnomAD-2.1.1 | 4.65E-05 | None | None | None | None | N | None | 8.27E-05 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.82E-05 | 0 |
| R/Q | rs200128066 |
0.153 | 1.0 | N | 0.507 | 0.269 | None | gnomAD-3.1.2 | 9.87E-05 | None | None | None | None | N | None | 7.25E-05 | 1.31406E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47141E-04 | 0 | 0 |
| R/Q | rs200128066 |
0.153 | 1.0 | N | 0.507 | 0.269 | None | gnomAD-4.0.0 | 8.12105E-05 | None | None | None | None | N | None | 5.34545E-05 | 6.67713E-05 | None | 0 | 2.22995E-05 | None | 1.56411E-05 | 0 | 1.00039E-04 | 0 | 4.80631E-05 |
| R/W | rs397517500 |
-0.363 | 1.0 | N | 0.61 | 0.585 | 0.476522311808 | gnomAD-2.1.1 | 9.65E-05 | None | None | None | None | N | None | 4.14E-05 | 1.4178E-04 | None | 9.67E-05 | 0 | None | 5.89082E-04 | None | 0 | 1.56E-05 | 0 |
| R/W | rs397517500 |
-0.363 | 1.0 | N | 0.61 | 0.585 | 0.476522311808 | gnomAD-3.1.2 | 1.18418E-04 | None | None | None | None | N | None | 4.83E-05 | 4.59318E-04 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 6.22148E-04 | 0 |
| R/W | rs397517500 |
-0.363 | 1.0 | N | 0.61 | 0.585 | 0.476522311808 | gnomAD-4.0.0 | 6.50913E-05 | None | None | None | None | N | None | 4.00716E-05 | 3.17079E-04 | None | 0 | 0 | None | 1.56402E-05 | 0 | 3.22167E-05 | 4.50312E-04 | 4.80677E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7158 | likely_pathogenic | 0.8736 | pathogenic | 0.196 | Stabilizing | 0.959 | D | 0.512 | neutral | None | None | None | None | N |
| R/C | 0.39 | ambiguous | 0.6228 | pathogenic | -0.112 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | N |
| R/D | 0.9006 | likely_pathogenic | 0.9604 | pathogenic | -0.225 | Destabilizing | 0.997 | D | 0.515 | neutral | None | None | None | None | N |
| R/E | 0.6858 | likely_pathogenic | 0.8292 | pathogenic | -0.156 | Destabilizing | 0.972 | D | 0.495 | neutral | None | None | None | None | N |
| R/F | 0.6578 | likely_pathogenic | 0.7996 | pathogenic | -0.05 | Destabilizing | 0.994 | D | 0.573 | neutral | None | None | None | None | N |
| R/G | 0.5679 | likely_pathogenic | 0.782 | pathogenic | 0.016 | Stabilizing | 0.995 | D | 0.523 | neutral | N | 0.496157381 | None | None | N |
| R/H | 0.1668 | likely_benign | 0.2664 | benign | -0.604 | Destabilizing | 0.999 | D | 0.48 | neutral | None | None | None | None | N |
| R/I | 0.4583 | ambiguous | 0.6032 | pathogenic | 0.629 | Stabilizing | 0.419 | N | 0.391 | neutral | None | None | None | None | N |
| R/K | 0.1948 | likely_benign | 0.2862 | benign | 0.035 | Stabilizing | 0.931 | D | 0.469 | neutral | None | None | None | None | N |
| R/L | 0.3695 | ambiguous | 0.5388 | ambiguous | 0.629 | Stabilizing | 0.902 | D | 0.515 | neutral | N | 0.496965458 | None | None | N |
| R/M | 0.5113 | ambiguous | 0.6707 | pathogenic | 0.016 | Stabilizing | 0.994 | D | 0.522 | neutral | None | None | None | None | N |
| R/N | 0.835 | likely_pathogenic | 0.9278 | pathogenic | 0.075 | Stabilizing | 0.997 | D | 0.459 | neutral | None | None | None | None | N |
| R/P | 0.7241 | likely_pathogenic | 0.881 | pathogenic | 0.504 | Stabilizing | 1.0 | D | 0.561 | neutral | N | 0.451809171 | None | None | N |
| R/Q | 0.2018 | likely_benign | 0.3158 | benign | 0.082 | Stabilizing | 1.0 | D | 0.507 | neutral | N | 0.483092084 | None | None | N |
| R/S | 0.768 | likely_pathogenic | 0.8975 | pathogenic | -0.078 | Destabilizing | 0.966 | D | 0.535 | neutral | None | None | None | None | N |
| R/T | 0.6171 | likely_pathogenic | 0.7994 | pathogenic | 0.117 | Stabilizing | 0.429 | N | 0.281 | neutral | None | None | None | None | N |
| R/V | 0.5728 | likely_pathogenic | 0.7384 | pathogenic | 0.504 | Stabilizing | 0.894 | D | 0.507 | neutral | None | None | None | None | N |
| R/W | 0.2451 | likely_benign | 0.3631 | ambiguous | -0.233 | Destabilizing | 1.0 | D | 0.61 | neutral | N | 0.497217354 | None | None | N |
| R/Y | 0.4847 | ambiguous | 0.6619 | pathogenic | 0.193 | Stabilizing | 0.998 | D | 0.563 | 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.