Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6601 | 20026;20027;20028 | chr2:178727777;178727776;178727775 | chr2:179592504;179592503;179592502 |
| N2AB | 6284 | 19075;19076;19077 | chr2:178727777;178727776;178727775 | chr2:179592504;179592503;179592502 |
| N2A | 5357 | 16294;16295;16296 | chr2:178727777;178727776;178727775 | chr2:179592504;179592503;179592502 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.942 | D | 0.619 | 0.725 | 0.551384154659 | gnomAD-4.0.0 | 6.84477E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65733E-05 |
| P/Q | rs1578111426  |
None | 0.126 | D | 0.311 | 0.638 | 0.398133443147 | gnomAD-4.0.0 | 6.84477E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99771E-07 | 0 | 0 |
| P/S | rs1175980116 |
-0.379 | 0.698 | D | 0.502 | 0.602 | 0.490144168196 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| P/S | rs1175980116 |
-0.379 | 0.698 | D | 0.502 | 0.602 | 0.490144168196 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| P/S | rs1175980116 |
-0.379 | 0.698 | D | 0.502 | 0.602 | 0.490144168196 | gnomAD-4.0.0 | 6.81922E-06 | None | None | None | None | I | None | 2.67123E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93521E-06 | 0 | 3.20349E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.076 | likely_benign | 0.0813 | benign | -0.537 | Destabilizing | 0.058 | N | 0.243 | neutral | N | 0.51290357 | None | None | I |
| P/C | 0.5997 | likely_pathogenic | 0.6292 | pathogenic | -0.762 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/D | 0.5101 | ambiguous | 0.5973 | pathogenic | -0.343 | Destabilizing | 0.956 | D | 0.507 | neutral | None | None | None | None | I |
| P/E | 0.263 | likely_benign | 0.2981 | benign | -0.434 | Destabilizing | 0.754 | D | 0.517 | neutral | None | None | None | None | I |
| P/F | 0.4534 | ambiguous | 0.4932 | ambiguous | -0.688 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | I |
| P/G | 0.3652 | ambiguous | 0.4337 | ambiguous | -0.665 | Destabilizing | 0.86 | D | 0.518 | neutral | None | None | None | None | I |
| P/H | 0.2058 | likely_benign | 0.2414 | benign | -0.081 | Destabilizing | 0.994 | D | 0.581 | neutral | None | None | None | None | I |
| P/I | 0.2925 | likely_benign | 0.285 | benign | -0.337 | Destabilizing | 0.978 | D | 0.675 | neutral | None | None | None | None | I |
| P/K | 0.2861 | likely_benign | 0.3159 | benign | -0.497 | Destabilizing | 0.754 | D | 0.477 | neutral | None | None | None | None | I |
| P/L | 0.1075 | likely_benign | 0.1099 | benign | -0.337 | Destabilizing | 0.942 | D | 0.619 | neutral | D | 0.605974315 | None | None | I |
| P/M | 0.2826 | likely_benign | 0.2891 | benign | -0.58 | Destabilizing | 0.994 | D | 0.582 | neutral | None | None | None | None | I |
| P/N | 0.377 | ambiguous | 0.4284 | ambiguous | -0.321 | Destabilizing | 0.956 | D | 0.604 | neutral | None | None | None | None | I |
| P/Q | 0.1391 | likely_benign | 0.1561 | benign | -0.519 | Destabilizing | 0.126 | N | 0.311 | neutral | D | 0.546149565 | None | None | I |
| P/R | 0.192 | likely_benign | 0.2127 | benign | 0.009 | Stabilizing | 0.89 | D | 0.601 | neutral | D | 0.631108818 | None | None | I |
| P/S | 0.1169 | likely_benign | 0.1328 | benign | -0.679 | Destabilizing | 0.698 | D | 0.502 | neutral | D | 0.53066543 | None | None | I |
| P/T | 0.1147 | likely_benign | 0.1224 | benign | -0.667 | Destabilizing | 0.942 | D | 0.495 | neutral | D | 0.57329982 | None | None | I |
| P/V | 0.1971 | likely_benign | 0.1931 | benign | -0.372 | Destabilizing | 0.956 | D | 0.53 | neutral | None | None | None | None | I |
| P/W | 0.6785 | likely_pathogenic | 0.7208 | pathogenic | -0.752 | Destabilizing | 0.998 | D | 0.655 | neutral | None | None | None | None | I |
| P/Y | 0.4352 | ambiguous | 0.4763 | ambiguous | -0.476 | Destabilizing | 0.978 | D | 0.682 | prob.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.