Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2870 | 8833;8834;8835 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
| N2AB | 2870 | 8833;8834;8835 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
| N2A | 2870 | 8833;8834;8835 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
| N2B | 2824 | 8695;8696;8697 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
| Novex-1 | 2824 | 8695;8696;8697 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
| Novex-2 | 2824 | 8695;8696;8697 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
| Novex-3 | 2870 | 8833;8834;8835 | chr2:178770093;178770092;178770091 | chr2:179634820;179634819;179634818 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/K | None | None | 0.826 | N | 0.407 | 0.39 | 0.262662153117 | gnomAD-4.0.0 | 1.59047E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85644E-06 | 0 | 0 |
| Q/L | rs372008728  |
0.177 | 0.959 | N | 0.49 | 0.529 | None | gnomAD-2.1.1 | 7.96E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.9857E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| Q/L | rs372008728 |
0.177 | 0.959 | N | 0.49 | 0.529 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Q/L | rs372008728 |
0.177 | 0.959 | N | 0.49 | 0.529 | None | gnomAD-4.0.0 | 2.47824E-06 | None | None | None | None | I | None | 0 | 0 | None | 1.35108E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.2021 | likely_benign | 0.217 | benign | -0.192 | Destabilizing | 0.927 | D | 0.428 | neutral | None | None | None | None | I |
| Q/C | 0.6925 | likely_pathogenic | 0.7442 | pathogenic | -0.5 | Destabilizing | 0.999 | D | 0.504 | neutral | None | None | None | None | I |
| Q/D | 0.2328 | likely_benign | 0.2431 | benign | -0.412 | Destabilizing | 0.969 | D | 0.374 | neutral | None | None | None | None | I |
| Q/E | 0.0968 | likely_benign | 0.097 | benign | -0.472 | Destabilizing | 0.826 | D | 0.357 | neutral | N | 0.428754132 | None | None | I |
| Q/F | 0.6737 | likely_pathogenic | 0.7149 | pathogenic | -0.675 | Destabilizing | 0.991 | D | 0.501 | neutral | None | None | None | None | I |
| Q/G | 0.2354 | likely_benign | 0.2576 | benign | -0.24 | Destabilizing | 0.969 | D | 0.503 | neutral | None | None | None | None | I |
| Q/H | 0.1631 | likely_benign | 0.1775 | benign | 0.012 | Stabilizing | 0.015 | N | 0.218 | neutral | N | 0.440460845 | None | None | I |
| Q/I | 0.4277 | ambiguous | 0.4722 | ambiguous | -0.155 | Destabilizing | 0.997 | D | 0.506 | neutral | None | None | None | None | I |
| Q/K | 0.0785 | likely_benign | 0.0881 | benign | -0.304 | Destabilizing | 0.826 | D | 0.407 | neutral | N | 0.471977519 | None | None | I |
| Q/L | 0.1452 | likely_benign | 0.1584 | benign | -0.155 | Destabilizing | 0.959 | D | 0.49 | neutral | N | 0.509940042 | None | None | I |
| Q/M | 0.3526 | ambiguous | 0.3854 | ambiguous | -0.265 | Destabilizing | 0.997 | D | 0.401 | neutral | None | None | None | None | I |
| Q/N | 0.1638 | likely_benign | 0.175 | benign | -0.587 | Destabilizing | 0.939 | D | 0.375 | neutral | None | None | None | None | I |
| Q/P | 0.1149 | likely_benign | 0.1129 | benign | -0.149 | Destabilizing | 0.996 | D | 0.461 | neutral | N | 0.5052277 | None | None | I |
| Q/R | 0.1062 | likely_benign | 0.1181 | benign | -0.086 | Destabilizing | 0.92 | D | 0.405 | neutral | N | 0.50517243 | None | None | I |
| Q/S | 0.1832 | likely_benign | 0.1864 | benign | -0.555 | Destabilizing | 0.969 | D | 0.366 | neutral | None | None | None | None | I |
| Q/T | 0.1718 | likely_benign | 0.1847 | benign | -0.518 | Destabilizing | 0.969 | D | 0.483 | neutral | None | None | None | None | I |
| Q/V | 0.3111 | likely_benign | 0.3397 | benign | -0.149 | Destabilizing | 0.99 | D | 0.499 | neutral | None | None | None | None | I |
| Q/W | 0.6219 | likely_pathogenic | 0.6738 | pathogenic | -0.786 | Destabilizing | 0.999 | D | 0.522 | neutral | None | None | None | None | I |
| Q/Y | 0.4671 | ambiguous | 0.5078 | ambiguous | -0.505 | Destabilizing | 0.939 | D | 0.469 | 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.