Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33751 | 101476;101477;101478 | chr2:178535364;178535363;178535362 | chr2:179400091;179400090;179400089 |
| N2AB | 32110 | 96553;96554;96555 | chr2:178535364;178535363;178535362 | chr2:179400091;179400090;179400089 |
| N2A | 31183 | 93772;93773;93774 | chr2:178535364;178535363;178535362 | chr2:179400091;179400090;179400089 |
| N2B | 24686 | 74281;74282;74283 | chr2:178535364;178535363;178535362 | chr2:179400091;179400090;179400089 |
| Novex-1 | 24811 | 74656;74657;74658 | chr2:178535364;178535363;178535362 | chr2:179400091;179400090;179400089 |
| Novex-2 | 24878 | 74857;74858;74859 | chr2:178535364;178535363;178535362 | chr2:179400091;179400090;179400089 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs753658469  |
-0.187 | 0.999 | N | 0.668 | 0.522 | None | gnomAD-2.1.1 | 2.85E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.24E-05 | 0 |
| N/H | rs753658469 |
-0.187 | 0.999 | N | 0.668 | 0.522 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.02878E-04 | 0 | 0 |
| N/H | rs753658469 |
-0.187 | 0.999 | N | 0.668 | 0.522 | None | gnomAD-4.0.0 | 2.78835E-05 | None | None | None | None | N | None | 1.33444E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.64448E-05 | 0 | 1.60087E-05 |
| N/S | rs1475672598 |
0.154 | 0.98 | N | 0.533 | 0.288 | 0.28798054836 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs1475672598 |
0.154 | 0.98 | N | 0.533 | 0.288 | 0.28798054836 | gnomAD-4.0.0 | 1.59107E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8578E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.5303 | ambiguous | 0.6143 | pathogenic | -0.325 | Destabilizing | 0.987 | D | 0.651 | neutral | None | None | None | None | N |
| N/C | 0.5258 | ambiguous | 0.6141 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| N/D | 0.5684 | likely_pathogenic | 0.514 | ambiguous | 0.422 | Stabilizing | 0.98 | D | 0.592 | neutral | N | 0.479888702 | None | None | N |
| N/E | 0.9005 | likely_pathogenic | 0.8951 | pathogenic | 0.406 | Stabilizing | 0.995 | D | 0.673 | neutral | None | None | None | None | N |
| N/F | 0.9271 | likely_pathogenic | 0.9396 | pathogenic | -0.723 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| N/G | 0.3765 | ambiguous | 0.4156 | ambiguous | -0.493 | Destabilizing | 0.998 | D | 0.513 | neutral | None | None | None | None | N |
| N/H | 0.2842 | likely_benign | 0.2865 | benign | -0.353 | Destabilizing | 0.999 | D | 0.668 | neutral | N | 0.482861037 | None | None | N |
| N/I | 0.8893 | likely_pathogenic | 0.9121 | pathogenic | 0.027 | Stabilizing | 0.999 | D | 0.677 | prob.neutral | D | 0.526680098 | None | None | N |
| N/K | 0.9016 | likely_pathogenic | 0.8918 | pathogenic | 0.177 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.486452102 | None | None | N |
| N/L | 0.7159 | likely_pathogenic | 0.7803 | pathogenic | 0.027 | Stabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| N/M | 0.8249 | likely_pathogenic | 0.8629 | pathogenic | 0.092 | Stabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | N |
| N/P | 0.8682 | likely_pathogenic | 0.8898 | pathogenic | -0.064 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | N |
| N/Q | 0.7114 | likely_pathogenic | 0.7348 | pathogenic | -0.261 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | N |
| N/R | 0.8603 | likely_pathogenic | 0.8554 | pathogenic | 0.241 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| N/S | 0.0956 | likely_benign | 0.1226 | benign | -0.174 | Destabilizing | 0.98 | D | 0.533 | neutral | N | 0.516177576 | None | None | N |
| N/T | 0.4107 | ambiguous | 0.5067 | ambiguous | -0.036 | Destabilizing | 0.987 | D | 0.671 | neutral | N | 0.496205579 | None | None | N |
| N/V | 0.8484 | likely_pathogenic | 0.888 | pathogenic | -0.064 | Destabilizing | 0.989 | D | 0.645 | neutral | None | None | None | None | N |
| N/W | 0.9657 | likely_pathogenic | 0.9667 | pathogenic | -0.734 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| N/Y | 0.5698 | likely_pathogenic | 0.5767 | pathogenic | -0.441 | Destabilizing | 1.0 | D | 0.65 | neutral | N | 0.508322353 | 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.