Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29888 | 89887;89888;89889 | chr2:178553238;178553237;178553236 | chr2:179417965;179417964;179417963 |
| N2AB | 28247 | 84964;84965;84966 | chr2:178553238;178553237;178553236 | chr2:179417965;179417964;179417963 |
| N2A | 27320 | 82183;82184;82185 | chr2:178553238;178553237;178553236 | chr2:179417965;179417964;179417963 |
| N2B | 20823 | 62692;62693;62694 | chr2:178553238;178553237;178553236 | chr2:179417965;179417964;179417963 |
| Novex-1 | 20948 | 63067;63068;63069 | chr2:178553238;178553237;178553236 | chr2:179417965;179417964;179417963 |
| Novex-2 | 21015 | 63268;63269;63270 | chr2:178553238;178553237;178553236 | chr2:179417965;179417964;179417963 |
| 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/M | rs1221359363  |
-0.794 | 1.0 | N | 0.717 | 0.449 | 0.629173233237 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| I/M | rs1221359363 |
-0.794 | 1.0 | N | 0.717 | 0.449 | 0.629173233237 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 0 |
| I/M | rs1221359363 |
-0.794 | 1.0 | N | 0.717 | 0.449 | 0.629173233237 | gnomAD-4.0.0 | 4.33868E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.6442E-04 | 4.23784E-06 | 0 | 1.60097E-05 |
| I/T | rs1700084788 |
None | 1.0 | N | 0.713 | 0.67 | 0.811166881841 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1700084788 |
None | 1.0 | N | 0.713 | 0.67 | 0.811166881841 | gnomAD-4.0.0 | 4.33865E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.14525E-05 | 0 | 4.23787E-06 | 0 | 0 |
| I/V | rs1301171033 |
None | 0.993 | N | 0.328 | 0.174 | 0.561905760881 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1301171033 |
None | 0.993 | N | 0.328 | 0.174 | 0.561905760881 | gnomAD-4.0.0 | 2.56337E-06 | None | None | None | None | N | None | 0 | 0 | None | 8.17996E-05 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4728 | ambiguous | 0.4196 | ambiguous | -1.753 | Destabilizing | 0.999 | D | 0.517 | neutral | None | None | None | None | N |
| I/C | 0.8156 | likely_pathogenic | 0.8052 | pathogenic | -1.157 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | N |
| I/D | 0.9634 | likely_pathogenic | 0.9475 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| I/E | 0.8636 | likely_pathogenic | 0.8256 | pathogenic | -0.87 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/F | 0.249 | likely_benign | 0.2465 | benign | -1.158 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.510397311 | None | None | N |
| I/G | 0.8921 | likely_pathogenic | 0.8625 | pathogenic | -2.124 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/H | 0.8096 | likely_pathogenic | 0.7821 | pathogenic | -1.312 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| I/K | 0.6878 | likely_pathogenic | 0.6406 | pathogenic | -1.111 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| I/L | 0.1802 | likely_benign | 0.1718 | benign | -0.79 | Destabilizing | 0.993 | D | 0.333 | neutral | N | 0.491657492 | None | None | N |
| I/M | 0.1287 | likely_benign | 0.1286 | benign | -0.692 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.502470819 | None | None | N |
| I/N | 0.7749 | likely_pathogenic | 0.7179 | pathogenic | -0.971 | Destabilizing | 1.0 | D | 0.813 | deleterious | D | 0.562205315 | None | None | N |
| I/P | 0.9391 | likely_pathogenic | 0.9078 | pathogenic | -1.08 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| I/Q | 0.7085 | likely_pathogenic | 0.6671 | pathogenic | -1.078 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| I/R | 0.5483 | ambiguous | 0.4984 | ambiguous | -0.617 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| I/S | 0.5854 | likely_pathogenic | 0.5272 | ambiguous | -1.686 | Destabilizing | 1.0 | D | 0.752 | deleterious | D | 0.522109238 | None | None | N |
| I/T | 0.2715 | likely_benign | 0.2168 | benign | -1.51 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.517487656 | None | None | N |
| I/V | 0.0888 | likely_benign | 0.0826 | benign | -1.08 | Destabilizing | 0.993 | D | 0.328 | neutral | N | 0.487937756 | None | None | N |
| I/W | 0.8482 | likely_pathogenic | 0.8278 | pathogenic | -1.232 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| I/Y | 0.7222 | likely_pathogenic | 0.6999 | pathogenic | -0.997 | Destabilizing | 1.0 | D | 0.772 | 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.