Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16714 | 50365;50366;50367 | chr2:178612385;178612384;178612383 | chr2:179477112;179477111;179477110 |
| N2AB | 15073 | 45442;45443;45444 | chr2:178612385;178612384;178612383 | chr2:179477112;179477111;179477110 |
| N2A | 14146 | 42661;42662;42663 | chr2:178612385;178612384;178612383 | chr2:179477112;179477111;179477110 |
| N2B | 7649 | 23170;23171;23172 | chr2:178612385;178612384;178612383 | chr2:179477112;179477111;179477110 |
| Novex-1 | 7774 | 23545;23546;23547 | chr2:178612385;178612384;178612383 | chr2:179477112;179477111;179477110 |
| Novex-2 | 7841 | 23746;23747;23748 | chr2:178612385;178612384;178612383 | chr2:179477112;179477111;179477110 |
| 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 | rs1309789816  |
0.216 | 1.0 | N | 0.665 | 0.462 | 0.675375996808 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| P/L | rs1309789816 |
0.216 | 1.0 | N | 0.665 | 0.462 | 0.675375996808 | gnomAD-4.0.0 | 2.05411E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69959E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.4894 | ambiguous | 0.5159 | ambiguous | -0.523 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.479159079 | None | None | N |
| P/C | 0.9615 | likely_pathogenic | 0.9708 | pathogenic | -0.627 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| P/D | 0.9165 | likely_pathogenic | 0.9316 | pathogenic | -0.414 | Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| P/E | 0.8951 | likely_pathogenic | 0.9165 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| P/F | 0.9825 | likely_pathogenic | 0.9845 | pathogenic | -0.695 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| P/G | 0.724 | likely_pathogenic | 0.7542 | pathogenic | -0.669 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| P/H | 0.8588 | likely_pathogenic | 0.8773 | pathogenic | -0.179 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| P/I | 0.9428 | likely_pathogenic | 0.9492 | pathogenic | -0.28 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| P/K | 0.951 | likely_pathogenic | 0.967 | pathogenic | -0.508 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/L | 0.8043 | likely_pathogenic | 0.8084 | pathogenic | -0.28 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.506408803 | None | None | N |
| P/M | 0.9259 | likely_pathogenic | 0.9293 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| P/N | 0.7955 | likely_pathogenic | 0.8319 | pathogenic | -0.245 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| P/Q | 0.8045 | likely_pathogenic | 0.8226 | pathogenic | -0.484 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.46823939 | None | None | N |
| P/R | 0.8997 | likely_pathogenic | 0.9226 | pathogenic | 0.037 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.44944377 | None | None | N |
| P/S | 0.6207 | likely_pathogenic | 0.6521 | pathogenic | -0.604 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.447124907 | None | None | N |
| P/T | 0.6501 | likely_pathogenic | 0.6608 | pathogenic | -0.605 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.475483706 | None | None | N |
| P/V | 0.8567 | likely_pathogenic | 0.8664 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| P/W | 0.9927 | likely_pathogenic | 0.9939 | pathogenic | -0.778 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| P/Y | 0.967 | likely_pathogenic | 0.9743 | pathogenic | -0.484 | Destabilizing | 1.0 | D | 0.688 | prob.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.