Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25663 | 77212;77213;77214 | chr2:178569145;178569144;178569143 | chr2:179433872;179433871;179433870 |
| N2AB | 24022 | 72289;72290;72291 | chr2:178569145;178569144;178569143 | chr2:179433872;179433871;179433870 |
| N2A | 23095 | 69508;69509;69510 | chr2:178569145;178569144;178569143 | chr2:179433872;179433871;179433870 |
| N2B | 16598 | 50017;50018;50019 | chr2:178569145;178569144;178569143 | chr2:179433872;179433871;179433870 |
| Novex-1 | 16723 | 50392;50393;50394 | chr2:178569145;178569144;178569143 | chr2:179433872;179433871;179433870 |
| Novex-2 | 16790 | 50593;50594;50595 | chr2:178569145;178569144;178569143 | chr2:179433872;179433871;179433870 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs143186270  |
-0.296 | 0.317 | N | 0.537 | 0.206 | None | gnomAD-2.1.1 | 1.46594E-04 | None | None | None | None | N | None | 9.92392E-04 | 8.49E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.0179E-04 | 1.40766E-04 |
| D/N | rs143186270 |
-0.296 | 0.317 | N | 0.537 | 0.206 | None | gnomAD-3.1.2 | 3.41934E-04 | None | None | None | None | N | None | 9.89526E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.4705E-04 | 0 | 4.78927E-04 |
| D/N | rs143186270 |
-0.296 | 0.317 | N | 0.537 | 0.206 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs143186270 |
-0.296 | 0.317 | N | 0.537 | 0.206 | None | gnomAD-4.0.0 | 1.35122E-04 | None | None | None | None | N | None | 9.86719E-04 | 3.335E-05 | None | 0 | 0 | None | 0 | 0 | 1.16147E-04 | 0 | 8.00615E-05 |
| D/Y | rs143186270 |
-0.217 | 0.973 | N | 0.779 | 0.425 | 0.578877614382 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 1.78E-05 | 0 |
| D/Y | rs143186270 |
-0.217 | 0.973 | N | 0.779 | 0.425 | 0.578877614382 | gnomAD-4.0.0 | 7.52829E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99648E-06 | 1.16031E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1132 | likely_benign | 0.1474 | benign | -0.475 | Destabilizing | 0.085 | N | 0.595 | neutral | N | 0.466404807 | None | None | N |
| D/C | 0.4383 | ambiguous | 0.5185 | ambiguous | -0.165 | Destabilizing | 0.852 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/E | 0.0824 | likely_benign | 0.0999 | benign | -0.625 | Destabilizing | None | N | 0.223 | neutral | N | 0.43536156 | None | None | N |
| D/F | 0.4781 | ambiguous | 0.568 | pathogenic | -0.157 | Destabilizing | 0.95 | D | 0.779 | deleterious | None | None | None | None | N |
| D/G | 0.111 | likely_benign | 0.1332 | benign | -0.782 | Destabilizing | 0.118 | N | 0.599 | neutral | N | 0.49131363 | None | None | N |
| D/H | 0.2301 | likely_benign | 0.2672 | benign | -0.355 | Destabilizing | 0.944 | D | 0.737 | prob.delet. | N | 0.472672231 | None | None | N |
| D/I | 0.2479 | likely_benign | 0.3052 | benign | 0.318 | Stabilizing | 0.862 | D | 0.789 | deleterious | None | None | None | None | N |
| D/K | 0.2758 | likely_benign | 0.3523 | ambiguous | -0.221 | Destabilizing | 0.306 | N | 0.559 | neutral | None | None | None | None | N |
| D/L | 0.234 | likely_benign | 0.2932 | benign | 0.318 | Stabilizing | 0.755 | D | 0.765 | deleterious | None | None | None | None | N |
| D/M | 0.4138 | ambiguous | 0.505 | ambiguous | 0.655 | Stabilizing | 0.964 | D | 0.757 | deleterious | None | None | None | None | N |
| D/N | 0.0888 | likely_benign | 0.1023 | benign | -0.631 | Destabilizing | 0.317 | N | 0.537 | neutral | N | 0.488753328 | None | None | N |
| D/P | 0.2847 | likely_benign | 0.3956 | ambiguous | 0.078 | Stabilizing | 0.11 | N | 0.738 | prob.delet. | None | None | None | None | N |
| D/Q | 0.1995 | likely_benign | 0.257 | benign | -0.52 | Destabilizing | 0.366 | N | 0.579 | neutral | None | None | None | None | N |
| D/R | 0.3454 | ambiguous | 0.4174 | ambiguous | -0.022 | Destabilizing | 0.607 | D | 0.751 | deleterious | None | None | None | None | N |
| D/S | 0.0819 | likely_benign | 0.096 | benign | -0.807 | Destabilizing | 0.109 | N | 0.452 | neutral | None | None | None | None | N |
| D/T | 0.1287 | likely_benign | 0.1593 | benign | -0.561 | Destabilizing | 0.277 | N | 0.675 | neutral | None | None | None | None | N |
| D/V | 0.1559 | likely_benign | 0.1912 | benign | 0.078 | Stabilizing | 0.29 | N | 0.754 | deleterious | N | 0.505608292 | None | None | N |
| D/W | 0.8261 | likely_pathogenic | 0.8761 | pathogenic | 0.022 | Stabilizing | 0.986 | D | 0.696 | prob.neutral | None | None | None | None | N |
| D/Y | 0.2371 | likely_benign | 0.2696 | benign | 0.076 | Stabilizing | 0.973 | D | 0.779 | deleterious | N | 0.494170301 | 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.