Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35786 | 107581;107582;107583 | chr2:178528295;178528294;178528293 | chr2:179393022;179393021;179393020 |
| N2AB | 34145 | 102658;102659;102660 | chr2:178528295;178528294;178528293 | chr2:179393022;179393021;179393020 |
| N2A | 33218 | 99877;99878;99879 | chr2:178528295;178528294;178528293 | chr2:179393022;179393021;179393020 |
| N2B | 26721 | 80386;80387;80388 | chr2:178528295;178528294;178528293 | chr2:179393022;179393021;179393020 |
| Novex-1 | 26846 | 80761;80762;80763 | chr2:178528295;178528294;178528293 | chr2:179393022;179393021;179393020 |
| Novex-2 | 26913 | 80962;80963;80964 | chr2:178528295;178528294;178528293 | chr2:179393022;179393021;179393020 |
| 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/I | rs749086389  |
-0.082 | 1.0 | N | 0.883 | 0.519 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 1.24008E-04 | 0 | None | 0 | 5.12E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs749086389 |
-0.082 | 1.0 | N | 0.883 | 0.519 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | I | None | 2.17098E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs749086389 |
-0.082 | 1.0 | N | 0.883 | 0.519 | None | gnomAD-4.0.0 | 1.30121E-05 | None | None | None | None | I | None | 1.99872E-04 | 0 | None | 0 | 2.22816E-05 | None | 0 | 0 | 2.54275E-06 | 0 | 3.20102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1271 | likely_benign | 0.1163 | benign | -0.602 | Destabilizing | 0.999 | D | 0.629 | neutral | D | 0.52563214 | None | None | I |
| T/C | 0.8045 | likely_pathogenic | 0.8299 | pathogenic | -0.288 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| T/D | 0.6651 | likely_pathogenic | 0.6214 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | I |
| T/E | 0.5177 | ambiguous | 0.4451 | ambiguous | -0.118 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| T/F | 0.5214 | ambiguous | 0.5226 | ambiguous | -0.956 | Destabilizing | 1.0 | D | 0.925 | deleterious | None | None | None | None | I |
| T/G | 0.5141 | ambiguous | 0.487 | ambiguous | -0.785 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| T/H | 0.5468 | ambiguous | 0.54 | ambiguous | -1.158 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | I |
| T/I | 0.3607 | ambiguous | 0.3715 | ambiguous | -0.225 | Destabilizing | 1.0 | D | 0.883 | deleterious | N | 0.488481168 | None | None | I |
| T/K | 0.4837 | ambiguous | 0.4323 | ambiguous | -0.532 | Destabilizing | 1.0 | D | 0.878 | deleterious | N | 0.517529944 | None | None | I |
| T/L | 0.2655 | likely_benign | 0.2735 | benign | -0.225 | Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | I |
| T/M | 0.148 | likely_benign | 0.1446 | benign | 0.138 | Stabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| T/N | 0.2643 | likely_benign | 0.2549 | benign | -0.328 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | I |
| T/P | 0.4108 | ambiguous | 0.3922 | ambiguous | -0.32 | Destabilizing | 1.0 | D | 0.879 | deleterious | N | 0.486354801 | None | None | I |
| T/Q | 0.4137 | ambiguous | 0.3711 | ambiguous | -0.584 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | I |
| T/R | 0.4141 | ambiguous | 0.3613 | ambiguous | -0.255 | Destabilizing | 1.0 | D | 0.883 | deleterious | N | 0.512337555 | None | None | I |
| T/S | 0.1555 | likely_benign | 0.1491 | benign | -0.567 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.432663263 | None | None | I |
| T/V | 0.2362 | likely_benign | 0.238 | benign | -0.32 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | I |
| T/W | 0.8769 | likely_pathogenic | 0.8699 | pathogenic | -0.902 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | I |
| T/Y | 0.6338 | likely_pathogenic | 0.6161 | pathogenic | -0.649 | Destabilizing | 1.0 | D | 0.917 | 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.