Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21090 | 63493;63494;63495 | chr2:178588139;178588138;178588137 | chr2:179452866;179452865;179452864 |
| N2AB | 19449 | 58570;58571;58572 | chr2:178588139;178588138;178588137 | chr2:179452866;179452865;179452864 |
| N2A | 18522 | 55789;55790;55791 | chr2:178588139;178588138;178588137 | chr2:179452866;179452865;179452864 |
| N2B | 12025 | 36298;36299;36300 | chr2:178588139;178588138;178588137 | chr2:179452866;179452865;179452864 |
| Novex-1 | 12150 | 36673;36674;36675 | chr2:178588139;178588138;178588137 | chr2:179452866;179452865;179452864 |
| Novex-2 | 12217 | 36874;36875;36876 | chr2:178588139;178588138;178588137 | chr2:179452866;179452865;179452864 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs377480514  |
-0.04 | 1.0 | N | 0.658 | 0.41 | 0.347217280506 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| Y/C | rs377480514 |
-0.04 | 1.0 | N | 0.658 | 0.41 | 0.347217280506 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| Y/C | rs377480514 |
-0.04 | 1.0 | N | 0.658 | 0.41 | 0.347217280506 | gnomAD-4.0.0 | 1.30314E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.56299E-05 | 0 | 1.5277E-05 | 0 | 3.20688E-05 |
| Y/F | rs377480514 |
-0.561 | 0.999 | N | 0.45 | 0.204 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| Y/F | rs377480514 |
-0.561 | 0.999 | N | 0.45 | 0.204 | None | gnomAD-4.0.0 | 1.43894E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.89147E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8653 | likely_pathogenic | 0.7554 | pathogenic | -0.701 | Destabilizing | 1.0 | D | 0.567 | neutral | None | None | None | None | I |
| Y/C | 0.4999 | ambiguous | 0.3784 | ambiguous | 0.016 | Stabilizing | 1.0 | D | 0.658 | neutral | N | 0.471857358 | None | None | I |
| Y/D | 0.7592 | likely_pathogenic | 0.6404 | pathogenic | 1.002 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.443217747 | None | None | I |
| Y/E | 0.9404 | likely_pathogenic | 0.881 | pathogenic | 0.985 | Stabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| Y/F | 0.2033 | likely_benign | 0.1287 | benign | -0.327 | Destabilizing | 0.999 | D | 0.45 | neutral | N | 0.488240748 | None | None | I |
| Y/G | 0.7927 | likely_pathogenic | 0.6629 | pathogenic | -0.882 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | I |
| Y/H | 0.6159 | likely_pathogenic | 0.4458 | ambiguous | 0.241 | Stabilizing | 1.0 | D | 0.638 | neutral | N | 0.497745665 | None | None | I |
| Y/I | 0.8951 | likely_pathogenic | 0.7945 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| Y/K | 0.8935 | likely_pathogenic | 0.837 | pathogenic | 0.167 | Stabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| Y/L | 0.8207 | likely_pathogenic | 0.7236 | pathogenic | -0.251 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | I |
| Y/M | 0.8796 | likely_pathogenic | 0.7821 | pathogenic | -0.116 | Destabilizing | 1.0 | D | 0.606 | neutral | None | None | None | None | I |
| Y/N | 0.5979 | likely_pathogenic | 0.4322 | ambiguous | -0.051 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.451261227 | None | None | I |
| Y/P | 0.9849 | likely_pathogenic | 0.9697 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| Y/Q | 0.8982 | likely_pathogenic | 0.8094 | pathogenic | None | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| Y/R | 0.7914 | likely_pathogenic | 0.7159 | pathogenic | 0.434 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| Y/S | 0.5938 | likely_pathogenic | 0.4447 | ambiguous | -0.514 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.445719334 | None | None | I |
| Y/T | 0.838 | likely_pathogenic | 0.6901 | pathogenic | -0.442 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| Y/V | 0.8081 | likely_pathogenic | 0.6825 | pathogenic | -0.381 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | I |
| Y/W | 0.6033 | likely_pathogenic | 0.5038 | ambiguous | -0.431 | Destabilizing | 1.0 | D | 0.623 | 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.