Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18819 | 56680;56681;56682 | chr2:178599338;178599337;178599336 | chr2:179464065;179464064;179464063 |
| N2AB | 17178 | 51757;51758;51759 | chr2:178599338;178599337;178599336 | chr2:179464065;179464064;179464063 |
| N2A | 16251 | 48976;48977;48978 | chr2:178599338;178599337;178599336 | chr2:179464065;179464064;179464063 |
| N2B | 9754 | 29485;29486;29487 | chr2:178599338;178599337;178599336 | chr2:179464065;179464064;179464063 |
| Novex-1 | 9879 | 29860;29861;29862 | chr2:178599338;178599337;178599336 | chr2:179464065;179464064;179464063 |
| Novex-2 | 9946 | 30061;30062;30063 | chr2:178599338;178599337;178599336 | chr2:179464065;179464064;179464063 |
| 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/K | rs1274184250  |
-0.432 | 0.996 | N | 0.499 | 0.304 | 0.117506650769 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.00007E-04 | None | 0 | 0 | 0 |
| N/K | rs1274184250 |
-0.432 | 0.996 | N | 0.499 | 0.304 | 0.117506650769 | gnomAD-4.0.0 | 4.801E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.34846E-05 | 0 |
| N/S | rs201337786 |
-1.161 | 0.905 | N | 0.394 | 0.17 | None | gnomAD-2.1.1 | 6.9E-05 | None | None | None | None | N | None | 7.06156E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.86205E-04 |
| N/S | rs201337786 |
-1.161 | 0.905 | N | 0.394 | 0.17 | None | gnomAD-3.1.2 | 1.25046E-04 | None | None | None | None | N | None | 3.86698E-04 | 1.31199E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| N/S | rs201337786 |
-1.161 | 0.905 | N | 0.394 | 0.17 | None | gnomAD-4.0.0 | 2.67163E-05 | None | None | None | None | N | None | 4.6814E-04 | 5.06244E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 8.02491E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.6154 | likely_pathogenic | 0.5136 | ambiguous | -1.014 | Destabilizing | 0.994 | D | 0.631 | neutral | None | None | None | None | N |
| N/C | 0.3929 | ambiguous | 0.3272 | benign | -0.568 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| N/D | 0.5067 | ambiguous | 0.3846 | ambiguous | -1.91 | Destabilizing | 0.996 | D | 0.475 | neutral | N | 0.519769668 | None | None | N |
| N/E | 0.9048 | likely_pathogenic | 0.8332 | pathogenic | -1.728 | Destabilizing | 0.997 | D | 0.508 | neutral | None | None | None | None | N |
| N/F | 0.8799 | likely_pathogenic | 0.8374 | pathogenic | -0.697 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| N/G | 0.4198 | ambiguous | 0.3625 | ambiguous | -1.366 | Destabilizing | 0.997 | D | 0.502 | neutral | None | None | None | None | N |
| N/H | 0.1936 | likely_benign | 0.1507 | benign | -0.992 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.492025706 | None | None | N |
| N/I | 0.9311 | likely_pathogenic | 0.877 | pathogenic | -0.096 | Destabilizing | 0.999 | D | 0.884 | deleterious | N | 0.479789029 | None | None | N |
| N/K | 0.8544 | likely_pathogenic | 0.7572 | pathogenic | -0.406 | Destabilizing | 0.996 | D | 0.499 | neutral | N | 0.501413194 | None | None | N |
| N/L | 0.8445 | likely_pathogenic | 0.7723 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| N/M | 0.8862 | likely_pathogenic | 0.8249 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| N/P | 0.9933 | likely_pathogenic | 0.9912 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| N/Q | 0.7816 | likely_pathogenic | 0.683 | pathogenic | -1.144 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| N/R | 0.7445 | likely_pathogenic | 0.6476 | pathogenic | -0.458 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | N |
| N/S | 0.1226 | likely_benign | 0.1052 | benign | -1.247 | Destabilizing | 0.905 | D | 0.394 | neutral | N | 0.46720462 | None | None | N |
| N/T | 0.6104 | likely_pathogenic | 0.4834 | ambiguous | -0.895 | Destabilizing | 0.992 | D | 0.484 | neutral | N | 0.512323621 | None | None | N |
| N/V | 0.8778 | likely_pathogenic | 0.8087 | pathogenic | -0.374 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| N/W | 0.9422 | likely_pathogenic | 0.9234 | pathogenic | -0.598 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| N/Y | 0.4421 | ambiguous | 0.3746 | ambiguous | -0.253 | Destabilizing | 1.0 | D | 0.872 | deleterious | N | 0.514017131 | 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.