Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25883 | 77872;77873;77874 | chr2:178568485;178568484;178568483 | chr2:179433212;179433211;179433210 |
| N2AB | 24242 | 72949;72950;72951 | chr2:178568485;178568484;178568483 | chr2:179433212;179433211;179433210 |
| N2A | 23315 | 70168;70169;70170 | chr2:178568485;178568484;178568483 | chr2:179433212;179433211;179433210 |
| N2B | 16818 | 50677;50678;50679 | chr2:178568485;178568484;178568483 | chr2:179433212;179433211;179433210 |
| Novex-1 | 16943 | 51052;51053;51054 | chr2:178568485;178568484;178568483 | chr2:179433212;179433211;179433210 |
| Novex-2 | 17010 | 51253;51254;51255 | chr2:178568485;178568484;178568483 | chr2:179433212;179433211;179433210 |
| 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/T | rs1158582678  |
-2.567 | 0.722 | D | 0.741 | 0.376 | 0.588411211809 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1158582678 |
-2.567 | 0.722 | D | 0.741 | 0.376 | 0.588411211809 | gnomAD-4.0.0 | 1.59207E-06 | None | None | None | None | N | None | 0 | 2.28749E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs769245498 |
-1.21 | 0.003 | N | 0.131 | 0.07 | 0.350524144436 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/V | rs769245498 |
-1.21 | 0.003 | N | 0.131 | 0.07 | 0.350524144436 | gnomAD-4.0.0 | 3.18413E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.8659E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5421 | ambiguous | 0.5913 | pathogenic | -2.155 | Highly Destabilizing | 0.415 | N | 0.656 | neutral | None | None | None | None | N |
| I/C | 0.7809 | likely_pathogenic | 0.793 | pathogenic | -1.606 | Destabilizing | 0.996 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/D | 0.9923 | likely_pathogenic | 0.9941 | pathogenic | -2.366 | Highly Destabilizing | 0.987 | D | 0.831 | deleterious | None | None | None | None | N |
| I/E | 0.9767 | likely_pathogenic | 0.9814 | pathogenic | -2.059 | Highly Destabilizing | 0.961 | D | 0.824 | deleterious | None | None | None | None | N |
| I/F | 0.1947 | likely_benign | 0.1851 | benign | -1.24 | Destabilizing | 0.82 | D | 0.701 | prob.neutral | D | 0.528133727 | None | None | N |
| I/G | 0.9338 | likely_pathogenic | 0.943 | pathogenic | -2.776 | Highly Destabilizing | 0.961 | D | 0.811 | deleterious | None | None | None | None | N |
| I/H | 0.9527 | likely_pathogenic | 0.9598 | pathogenic | -2.499 | Highly Destabilizing | 0.996 | D | 0.795 | deleterious | None | None | None | None | N |
| I/K | 0.9501 | likely_pathogenic | 0.9605 | pathogenic | -1.364 | Destabilizing | 0.961 | D | 0.816 | deleterious | None | None | None | None | N |
| I/L | 0.1093 | likely_benign | 0.1081 | benign | -0.322 | Destabilizing | 0.003 | N | 0.145 | neutral | N | 0.484956166 | None | None | N |
| I/M | 0.107 | likely_benign | 0.1106 | benign | -0.575 | Destabilizing | 0.959 | D | 0.693 | prob.neutral | N | 0.509054185 | None | None | N |
| I/N | 0.9364 | likely_pathogenic | 0.9473 | pathogenic | -1.923 | Destabilizing | 0.983 | D | 0.829 | deleterious | D | 0.527500835 | None | None | N |
| I/P | 0.974 | likely_pathogenic | 0.9796 | pathogenic | -0.917 | Destabilizing | 0.987 | D | 0.831 | deleterious | None | None | None | None | N |
| I/Q | 0.9438 | likely_pathogenic | 0.9522 | pathogenic | -1.59 | Destabilizing | 0.987 | D | 0.826 | deleterious | None | None | None | None | N |
| I/R | 0.9197 | likely_pathogenic | 0.9357 | pathogenic | -1.526 | Destabilizing | 0.961 | D | 0.829 | deleterious | None | None | None | None | N |
| I/S | 0.8202 | likely_pathogenic | 0.8547 | pathogenic | -2.648 | Highly Destabilizing | 0.949 | D | 0.771 | deleterious | N | 0.51150972 | None | None | N |
| I/T | 0.458 | ambiguous | 0.5364 | ambiguous | -2.159 | Highly Destabilizing | 0.722 | D | 0.741 | deleterious | D | 0.535675775 | None | None | N |
| I/V | 0.0699 | likely_benign | 0.0684 | benign | -0.917 | Destabilizing | 0.003 | N | 0.131 | neutral | N | 0.485129524 | None | None | N |
| I/W | 0.8883 | likely_pathogenic | 0.8978 | pathogenic | -1.612 | Destabilizing | 0.996 | D | 0.802 | deleterious | None | None | None | None | N |
| I/Y | 0.7963 | likely_pathogenic | 0.8121 | pathogenic | -1.286 | Destabilizing | 0.961 | D | 0.789 | deleterious | 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.