Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3067 | 9424;9425;9426 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
| N2AB | 3067 | 9424;9425;9426 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
| N2A | 3067 | 9424;9425;9426 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
| N2B | 3021 | 9286;9287;9288 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
| Novex-1 | 3021 | 9286;9287;9288 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
| Novex-2 | 3021 | 9286;9287;9288 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
| Novex-3 | 3067 | 9424;9425;9426 | chr2:178768120;178768119;178768118 | chr2:179632847;179632846;179632845 |
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/L | None | None | 0.993 | N | 0.33 | 0.294 | 0.588202069064 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| I/M | None | None | 1.0 | D | 0.674 | 0.365 | 0.513503867364 | gnomAD-4.0.0 | 1.59066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77716E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1435097269  |
-2.102 | 1.0 | N | 0.689 | 0.572 | 0.739398645562 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 8.68E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1435097269 |
-2.102 | 1.0 | N | 0.689 | 0.572 | 0.739398645562 | gnomAD-4.0.0 | 6.36266E-06 | None | None | None | None | N | None | 0 | 6.86059E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.0217E-05 |
| I/V | rs2154341582 |
None | 0.993 | N | 0.33 | 0.175 | 0.649418150632 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9216E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs2154341582 |
None | 0.993 | N | 0.33 | 0.175 | 0.649418150632 | gnomAD-4.0.0 | 6.56418E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.92604E-04 | 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 | 0.8303 | likely_pathogenic | 0.8768 | pathogenic | -1.731 | Destabilizing | 0.999 | D | 0.495 | neutral | None | None | None | None | N |
| I/C | 0.9376 | likely_pathogenic | 0.9535 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| I/D | 0.9841 | likely_pathogenic | 0.9873 | pathogenic | -1.208 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | N |
| I/E | 0.9083 | likely_pathogenic | 0.9288 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| I/F | 0.592 | likely_pathogenic | 0.6348 | pathogenic | -0.96 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | D | 0.600686246 | None | None | N |
| I/G | 0.9699 | likely_pathogenic | 0.9804 | pathogenic | -2.168 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/H | 0.9317 | likely_pathogenic | 0.9459 | pathogenic | -1.463 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| I/K | 0.8087 | likely_pathogenic | 0.8481 | pathogenic | -1.146 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| I/L | 0.2263 | likely_benign | 0.2765 | benign | -0.544 | Destabilizing | 0.993 | D | 0.33 | neutral | N | 0.489227862 | None | None | N |
| I/M | 0.1714 | likely_benign | 0.2094 | benign | -0.424 | Destabilizing | 1.0 | D | 0.674 | neutral | D | 0.533077054 | None | None | N |
| I/N | 0.8262 | likely_pathogenic | 0.8629 | pathogenic | -1.181 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.680691557 | None | None | N |
| I/P | 0.9952 | likely_pathogenic | 0.996 | pathogenic | -0.911 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| I/Q | 0.8024 | likely_pathogenic | 0.843 | pathogenic | -1.169 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| I/R | 0.7764 | likely_pathogenic | 0.8177 | pathogenic | -0.794 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| I/S | 0.8354 | likely_pathogenic | 0.8718 | pathogenic | -1.877 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.54450115 | None | None | N |
| I/T | 0.6283 | likely_pathogenic | 0.702 | pathogenic | -1.625 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.499148727 | None | None | N |
| I/V | 0.1378 | likely_benign | 0.152 | benign | -0.911 | Destabilizing | 0.993 | D | 0.33 | neutral | N | 0.476993142 | None | None | N |
| I/W | 0.9704 | likely_pathogenic | 0.976 | pathogenic | -1.206 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Y | 0.9157 | likely_pathogenic | 0.9297 | pathogenic | -0.894 | Destabilizing | 1.0 | D | 0.748 | 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.