Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19177 | 57754;57755;57756 | chr2:178597553;178597552;178597551 | chr2:179462280;179462279;179462278 |
| N2AB | 17536 | 52831;52832;52833 | chr2:178597553;178597552;178597551 | chr2:179462280;179462279;179462278 |
| N2A | 16609 | 50050;50051;50052 | chr2:178597553;178597552;178597551 | chr2:179462280;179462279;179462278 |
| N2B | 10112 | 30559;30560;30561 | chr2:178597553;178597552;178597551 | chr2:179462280;179462279;179462278 |
| Novex-1 | 10237 | 30934;30935;30936 | chr2:178597553;178597552;178597551 | chr2:179462280;179462279;179462278 |
| Novex-2 | 10304 | 31135;31136;31137 | chr2:178597553;178597552;178597551 | chr2:179462280;179462279;179462278 |
| 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/L | rs1338580543  |
-0.583 | 0.993 | N | 0.289 | 0.262 | 0.693807273274 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.71E-05 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs1338580543 |
-0.583 | 0.993 | N | 0.289 | 0.262 | 0.693807273274 | gnomAD-4.0.0 | 1.5959E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79501E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | None | None | 1.0 | N | 0.685 | 0.343 | 0.767533944701 | gnomAD-4.0.0 | 1.59609E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86393E-06 | 0 | 0 |
| I/V | rs1338580543 |
-0.866 | 0.993 | N | 0.285 | 0.198 | 0.668925388245 | gnomAD-2.1.1 | 7.21E-06 | None | None | None | None | N | None | 0 | 2.86E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.89E-06 | 0 |
| I/V | rs1338580543 |
-0.866 | 0.993 | N | 0.285 | 0.198 | 0.668925388245 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1338580543 |
-0.866 | 0.993 | N | 0.285 | 0.198 | 0.668925388245 | gnomAD-4.0.0 | 6.57505E-06 | None | None | None | None | N | None | 0 | 6.55652E-05 | None | 0 | 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 | 0.4076 | ambiguous | 0.3898 | ambiguous | -1.782 | Destabilizing | 0.999 | D | 0.535 | neutral | None | None | None | None | N |
| I/C | 0.8083 | likely_pathogenic | 0.8068 | pathogenic | -1.118 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| I/D | 0.888 | likely_pathogenic | 0.8879 | pathogenic | -1.021 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/E | 0.8025 | likely_pathogenic | 0.7946 | pathogenic | -0.967 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| I/F | 0.2541 | likely_benign | 0.2561 | benign | -1.11 | Destabilizing | 1.0 | D | 0.7 | prob.neutral | N | 0.48472688 | None | None | N |
| I/G | 0.8371 | likely_pathogenic | 0.8267 | pathogenic | -2.154 | Highly Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| I/H | 0.5997 | likely_pathogenic | 0.6266 | pathogenic | -1.325 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| I/K | 0.5833 | likely_pathogenic | 0.6076 | pathogenic | -1.149 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| I/L | 0.1554 | likely_benign | 0.1541 | benign | -0.809 | Destabilizing | 0.993 | D | 0.289 | neutral | N | 0.461119301 | None | None | N |
| I/M | 0.1285 | likely_benign | 0.1275 | benign | -0.682 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.511644122 | None | None | N |
| I/N | 0.4746 | ambiguous | 0.4818 | ambiguous | -1.043 | Destabilizing | 1.0 | D | 0.769 | deleterious | N | 0.4249665 | None | None | N |
| I/P | 0.9174 | likely_pathogenic | 0.9232 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| I/Q | 0.6196 | likely_pathogenic | 0.6142 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/R | 0.4338 | ambiguous | 0.4749 | ambiguous | -0.646 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| I/S | 0.4307 | ambiguous | 0.4291 | ambiguous | -1.763 | Destabilizing | 1.0 | D | 0.747 | deleterious | N | 0.45734549 | None | None | N |
| I/T | 0.1925 | likely_benign | 0.1782 | benign | -1.588 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.42598522 | None | None | N |
| I/V | 0.0996 | likely_benign | 0.0886 | benign | -1.103 | Destabilizing | 0.993 | D | 0.285 | neutral | N | 0.492538286 | None | None | N |
| I/W | 0.7963 | likely_pathogenic | 0.8234 | pathogenic | -1.207 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6158 | likely_pathogenic | 0.6611 | pathogenic | -0.969 | Destabilizing | 1.0 | D | 0.754 | 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.