Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31098 | 93517;93518;93519 | chr2:178548334;178548333;178548332 | chr2:179413061;179413060;179413059 |
| N2AB | 29457 | 88594;88595;88596 | chr2:178548334;178548333;178548332 | chr2:179413061;179413060;179413059 |
| N2A | 28530 | 85813;85814;85815 | chr2:178548334;178548333;178548332 | chr2:179413061;179413060;179413059 |
| N2B | 22033 | 66322;66323;66324 | chr2:178548334;178548333;178548332 | chr2:179413061;179413060;179413059 |
| Novex-1 | 22158 | 66697;66698;66699 | chr2:178548334;178548333;178548332 | chr2:179413061;179413060;179413059 |
| Novex-2 | 22225 | 66898;66899;66900 | chr2:178548334;178548333;178548332 | chr2:179413061;179413060;179413059 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.052 | N | 0.401 | 0.094 | 0.337378238328 | gnomAD-4.0.0 | 6.84183E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99436E-07 | 0 | 0 |
| V/D | rs886378576  |
None | 0.317 | N | 0.545 | 0.197 | 0.682257776623 | gnomAD-4.0.0 | 6.84183E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99436E-07 | 0 | 0 |
| V/I | rs760282296 |
-0.384 | None | N | 0.197 | 0.075 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | I | None | 2.47975E-04 | 1.41403E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs760282296 |
-0.384 | None | N | 0.197 | 0.075 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | I | None | 3.13661E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs760282296 |
-0.384 | None | N | 0.197 | 0.075 | None | gnomAD-4.0.0 | 1.85904E-05 | None | None | None | None | I | None | 2.93647E-04 | 1.0002E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0847 | likely_benign | 0.0828 | benign | -0.833 | Destabilizing | 0.052 | N | 0.401 | neutral | N | 0.478403048 | None | None | I |
| V/C | 0.4734 | ambiguous | 0.4765 | ambiguous | -0.775 | Destabilizing | 0.935 | D | 0.529 | neutral | None | None | None | None | I |
| V/D | 0.2136 | likely_benign | 0.2117 | benign | -0.513 | Destabilizing | 0.317 | N | 0.545 | neutral | N | 0.466987465 | None | None | I |
| V/E | 0.164 | likely_benign | 0.1723 | benign | -0.616 | Destabilizing | 0.081 | N | 0.506 | neutral | None | None | None | None | I |
| V/F | 0.1163 | likely_benign | 0.1149 | benign | -0.99 | Destabilizing | 0.317 | N | 0.539 | neutral | N | 0.513670415 | None | None | I |
| V/G | 0.146 | likely_benign | 0.141 | benign | -1.001 | Destabilizing | 0.211 | N | 0.546 | neutral | N | 0.484900683 | None | None | I |
| V/H | 0.3175 | likely_benign | 0.3232 | benign | -0.486 | Destabilizing | 0.824 | D | 0.574 | neutral | None | None | None | None | I |
| V/I | 0.0613 | likely_benign | 0.0639 | benign | -0.53 | Destabilizing | None | N | 0.197 | neutral | N | 0.42147233 | None | None | I |
| V/K | 0.1922 | likely_benign | 0.2001 | benign | -0.554 | Destabilizing | 0.001 | N | 0.366 | neutral | None | None | None | None | I |
| V/L | 0.1038 | likely_benign | 0.1042 | benign | -0.53 | Destabilizing | 0.009 | N | 0.341 | neutral | N | 0.496103374 | None | None | I |
| V/M | 0.0881 | likely_benign | 0.0904 | benign | -0.4 | Destabilizing | 0.38 | N | 0.54 | neutral | None | None | None | None | I |
| V/N | 0.1488 | likely_benign | 0.1543 | benign | -0.297 | Destabilizing | 0.555 | D | 0.551 | neutral | None | None | None | None | I |
| V/P | 0.1925 | likely_benign | 0.1899 | benign | -0.596 | Destabilizing | 0.791 | D | 0.56 | neutral | None | None | None | None | I |
| V/Q | 0.1855 | likely_benign | 0.1883 | benign | -0.597 | Destabilizing | 0.016 | N | 0.417 | neutral | None | None | None | None | I |
| V/R | 0.1687 | likely_benign | 0.1642 | benign | 0.018 | Stabilizing | 0.081 | N | 0.54 | neutral | None | None | None | None | I |
| V/S | 0.1173 | likely_benign | 0.1132 | benign | -0.737 | Destabilizing | 0.149 | N | 0.485 | neutral | None | None | None | None | I |
| V/T | 0.0876 | likely_benign | 0.0878 | benign | -0.739 | Destabilizing | 0.149 | N | 0.401 | neutral | None | None | None | None | I |
| V/W | 0.5708 | likely_pathogenic | 0.576 | pathogenic | -1.016 | Destabilizing | 0.935 | D | 0.625 | neutral | None | None | None | None | I |
| V/Y | 0.3413 | ambiguous | 0.3415 | ambiguous | -0.719 | Destabilizing | 0.555 | D | 0.537 | 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.