Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28439 | 85540;85541;85542 | chr2:178560817;178560816;178560815 | chr2:179425544;179425543;179425542 |
| N2AB | 26798 | 80617;80618;80619 | chr2:178560817;178560816;178560815 | chr2:179425544;179425543;179425542 |
| N2A | 25871 | 77836;77837;77838 | chr2:178560817;178560816;178560815 | chr2:179425544;179425543;179425542 |
| N2B | 19374 | 58345;58346;58347 | chr2:178560817;178560816;178560815 | chr2:179425544;179425543;179425542 |
| Novex-1 | 19499 | 58720;58721;58722 | chr2:178560817;178560816;178560815 | chr2:179425544;179425543;179425542 |
| Novex-2 | 19566 | 58921;58922;58923 | chr2:178560817;178560816;178560815 | chr2:179425544;179425543;179425542 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs764437671  |
0.305 | 0.922 | N | 0.644 | 0.385 | 0.617917861134 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/L | rs764437671 |
0.305 | 0.922 | N | 0.644 | 0.385 | 0.617917861134 | gnomAD-4.0.0 | 1.23172E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61908E-05 | 0 | 0 |
| R/P | None | None | 0.988 | N | 0.739 | 0.517 | 0.546693616777 | gnomAD-4.0.0 | 1.36858E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79898E-06 | 0 | 0 |
| R/Q | rs764437671 |
0.112 | 0.989 | D | 0.643 | 0.288 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 4.13E-05 | 5.67E-05 | None | 0 | 1.03125E-04 | None | 0 | None | 0 | 3.13E-05 | 0 |
| R/Q | rs764437671 |
0.112 | 0.989 | D | 0.643 | 0.288 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | I | None | 2.41E-05 | 1.31062E-04 | 0 | 0 | 5.79598E-04 | None | 0 | 0 | 5.88E-05 | 0 | 4.77555E-04 |
| R/Q | rs764437671 |
0.112 | 0.989 | D | 0.643 | 0.288 | None | gnomAD-4.0.0 | 2.60284E-05 | None | None | None | None | I | None | 2.66546E-05 | 8.33528E-05 | None | 0 | 1.11702E-04 | None | 0 | 0 | 1.61049E-05 | 6.58892E-05 | 8.00435E-05 |
| R/W | rs757653038 |
-0.519 | 1.0 | N | 0.753 | 0.484 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | I | None | 4.13E-05 | 1.98345E-04 | None | 0 | 5.16E-05 | None | 0 | None | 0 | 7.82E-06 | 0 |
| R/W | rs757653038 |
-0.519 | 1.0 | N | 0.753 | 0.484 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs757653038 |
-0.519 | 1.0 | N | 0.753 | 0.484 | None | gnomAD-4.0.0 | 1.73534E-05 | None | None | None | None | I | None | 1.33479E-05 | 1.5007E-04 | None | 0 | 0 | None | 0 | 0 | 1.35621E-05 | 1.09813E-05 | 1.60143E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3855 | ambiguous | 0.3662 | ambiguous | 0.004 | Stabilizing | 0.754 | D | 0.613 | neutral | None | None | None | None | I |
| R/C | 0.1992 | likely_benign | 0.1899 | benign | -0.275 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | I |
| R/D | 0.7678 | likely_pathogenic | 0.7401 | pathogenic | -0.158 | Destabilizing | 0.956 | D | 0.653 | neutral | None | None | None | None | I |
| R/E | 0.4611 | ambiguous | 0.4329 | ambiguous | -0.11 | Destabilizing | 0.754 | D | 0.579 | neutral | None | None | None | None | I |
| R/F | 0.6071 | likely_pathogenic | 0.5936 | pathogenic | -0.311 | Destabilizing | 0.993 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/G | 0.3615 | ambiguous | 0.3356 | benign | -0.15 | Destabilizing | 0.922 | D | 0.644 | neutral | N | 0.48703591 | None | None | I |
| R/H | 0.1432 | likely_benign | 0.1342 | benign | -0.603 | Destabilizing | 0.978 | D | 0.596 | neutral | None | None | None | None | I |
| R/I | 0.2776 | likely_benign | 0.2697 | benign | 0.365 | Stabilizing | 0.978 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/K | 0.1107 | likely_benign | 0.1171 | benign | -0.131 | Destabilizing | 0.008 | N | 0.198 | neutral | None | None | None | None | I |
| R/L | 0.2881 | likely_benign | 0.2692 | benign | 0.365 | Stabilizing | 0.922 | D | 0.644 | neutral | N | 0.48265459 | None | None | I |
| R/M | 0.2986 | likely_benign | 0.2925 | benign | -0.056 | Destabilizing | 0.998 | D | 0.643 | neutral | None | None | None | None | I |
| R/N | 0.632 | likely_pathogenic | 0.6119 | pathogenic | -0.026 | Destabilizing | 0.956 | D | 0.606 | neutral | None | None | None | None | I |
| R/P | 0.9409 | likely_pathogenic | 0.9353 | pathogenic | 0.264 | Stabilizing | 0.988 | D | 0.739 | prob.delet. | N | 0.510166594 | None | None | I |
| R/Q | 0.1289 | likely_benign | 0.1216 | benign | -0.088 | Destabilizing | 0.989 | D | 0.643 | neutral | D | 0.523706555 | None | None | I |
| R/S | 0.5072 | ambiguous | 0.4807 | ambiguous | -0.297 | Destabilizing | 0.86 | D | 0.644 | neutral | None | None | None | None | I |
| R/T | 0.2357 | likely_benign | 0.2336 | benign | -0.131 | Destabilizing | 0.86 | D | 0.63 | neutral | None | None | None | None | I |
| R/V | 0.3203 | likely_benign | 0.3141 | benign | 0.264 | Stabilizing | 0.956 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/W | 0.2911 | likely_benign | 0.2656 | benign | -0.445 | Destabilizing | 1.0 | D | 0.753 | deleterious | N | 0.510673573 | None | None | I |
| R/Y | 0.4523 | ambiguous | 0.4338 | ambiguous | -0.027 | Destabilizing | 0.993 | D | 0.741 | deleterious | 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.