Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26500 | 79723;79724;79725 | chr2:178566634;178566633;178566632 | chr2:179431361;179431360;179431359 |
| N2AB | 24859 | 74800;74801;74802 | chr2:178566634;178566633;178566632 | chr2:179431361;179431360;179431359 |
| N2A | 23932 | 72019;72020;72021 | chr2:178566634;178566633;178566632 | chr2:179431361;179431360;179431359 |
| N2B | 17435 | 52528;52529;52530 | chr2:178566634;178566633;178566632 | chr2:179431361;179431360;179431359 |
| Novex-1 | 17560 | 52903;52904;52905 | chr2:178566634;178566633;178566632 | chr2:179431361;179431360;179431359 |
| Novex-2 | 17627 | 53104;53105;53106 | chr2:178566634;178566633;178566632 | chr2:179431361;179431360;179431359 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs1172084404  |
-0.671 | 0.76 | N | 0.446 | 0.253 | 0.152612264143 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| T/A | rs1172084404 |
-0.671 | 0.76 | N | 0.446 | 0.253 | 0.152612264143 | gnomAD-4.0.0 | 2.05398E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69861E-06 | 0 | 0 |
| T/I | rs1480393355 |
0.053 | 0.991 | N | 0.485 | 0.498 | 0.393006254552 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.96E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1480393355 |
0.053 | 0.991 | N | 0.485 | 0.498 | 0.393006254552 | gnomAD-4.0.0 | 2.73885E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.82731E-05 | 2.51927E-05 | None | 0 | 0 | 1.79907E-06 | 0 | 0 |
| T/S | rs1480393355 |
-1.001 | 0.17 | N | 0.328 | 0.119 | 0.0762999501168 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs1480393355 |
-1.001 | 0.17 | N | 0.328 | 0.119 | 0.0762999501168 | gnomAD-4.0.0 | 1.36942E-06 | None | None | None | None | N | None | 0 | 2.23634E-05 | None | 0 | 0 | None | 0 | 0 | 8.99533E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1892 | likely_benign | 0.1682 | benign | -0.152 | Destabilizing | 0.76 | D | 0.446 | neutral | N | 0.472799319 | None | None | N |
| T/C | 0.637 | likely_pathogenic | 0.5264 | ambiguous | -0.467 | Destabilizing | 0.999 | D | 0.477 | neutral | None | None | None | None | N |
| T/D | 0.6697 | likely_pathogenic | 0.6084 | pathogenic | -1.82 | Destabilizing | 0.986 | D | 0.448 | neutral | None | None | None | None | N |
| T/E | 0.7443 | likely_pathogenic | 0.7078 | pathogenic | -1.81 | Destabilizing | 0.953 | D | 0.458 | neutral | None | None | None | None | N |
| T/F | 0.7633 | likely_pathogenic | 0.7004 | pathogenic | -0.606 | Destabilizing | 0.998 | D | 0.568 | neutral | None | None | None | None | N |
| T/G | 0.2159 | likely_benign | 0.1814 | benign | -0.37 | Destabilizing | 0.91 | D | 0.483 | neutral | None | None | None | None | N |
| T/H | 0.5127 | ambiguous | 0.4347 | ambiguous | -0.897 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| T/I | 0.8678 | likely_pathogenic | 0.8223 | pathogenic | 0.327 | Stabilizing | 0.991 | D | 0.485 | neutral | N | 0.499741892 | None | None | N |
| T/K | 0.5244 | ambiguous | 0.4905 | ambiguous | -0.531 | Destabilizing | 0.91 | D | 0.456 | neutral | None | None | None | None | N |
| T/L | 0.4415 | ambiguous | 0.3832 | ambiguous | 0.327 | Stabilizing | 0.953 | D | 0.457 | neutral | None | None | None | None | N |
| T/M | 0.3011 | likely_benign | 0.2588 | benign | 0.7 | Stabilizing | 0.999 | D | 0.469 | neutral | None | None | None | None | N |
| T/N | 0.2723 | likely_benign | 0.235 | benign | -0.95 | Destabilizing | 0.982 | D | 0.473 | neutral | N | 0.464099132 | None | None | N |
| T/P | 0.8404 | likely_pathogenic | 0.8257 | pathogenic | 0.199 | Stabilizing | 0.991 | D | 0.485 | neutral | N | 0.510337728 | None | None | N |
| T/Q | 0.4705 | ambiguous | 0.4369 | ambiguous | -1.229 | Destabilizing | 0.986 | D | 0.488 | neutral | None | None | None | None | N |
| T/R | 0.4586 | ambiguous | 0.4226 | ambiguous | -0.244 | Destabilizing | 0.128 | N | 0.346 | neutral | None | None | None | None | N |
| T/S | 0.1073 | likely_benign | 0.0866 | benign | -0.829 | Destabilizing | 0.17 | N | 0.328 | neutral | N | 0.476639674 | None | None | N |
| T/V | 0.6493 | likely_pathogenic | 0.5917 | pathogenic | 0.199 | Stabilizing | 0.953 | D | 0.46 | neutral | None | None | None | None | N |
| T/W | 0.91 | likely_pathogenic | 0.8814 | pathogenic | -0.775 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| T/Y | 0.7413 | likely_pathogenic | 0.6708 | pathogenic | -0.335 | Destabilizing | 0.998 | D | 0.575 | neutral | 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.