Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26158 | 78697;78698;78699 | chr2:178567660;178567659;178567658 | chr2:179432387;179432386;179432385 |
| N2AB | 24517 | 73774;73775;73776 | chr2:178567660;178567659;178567658 | chr2:179432387;179432386;179432385 |
| N2A | 23590 | 70993;70994;70995 | chr2:178567660;178567659;178567658 | chr2:179432387;179432386;179432385 |
| N2B | 17093 | 51502;51503;51504 | chr2:178567660;178567659;178567658 | chr2:179432387;179432386;179432385 |
| Novex-1 | 17218 | 51877;51878;51879 | chr2:178567660;178567659;178567658 | chr2:179432387;179432386;179432385 |
| Novex-2 | 17285 | 52078;52079;52080 | chr2:178567660;178567659;178567658 | chr2:179432387;179432386;179432385 |
| 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/K | None | None | None | N | 0.106 | 0.086 | 0.143124449307 | gnomAD-4.0.0 | 6.84868E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00171E-07 | 0 | 0 |
| R/T | rs1248526272  |
-0.599 | 0.324 | N | 0.372 | 0.236 | 0.357519025918 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| R/T | rs1248526272 |
-0.599 | 0.324 | N | 0.372 | 0.236 | 0.357519025918 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/T | rs1248526272 |
-0.599 | 0.324 | N | 0.372 | 0.236 | 0.357519025918 | gnomAD-4.0.0 | 2.48105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39298E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4109 | ambiguous | 0.4022 | ambiguous | -0.881 | Destabilizing | 0.116 | N | 0.367 | neutral | None | None | None | None | N |
| R/C | 0.1973 | likely_benign | 0.205 | benign | -0.857 | Destabilizing | 0.981 | D | 0.402 | neutral | None | None | None | None | N |
| R/D | 0.7532 | likely_pathogenic | 0.7514 | pathogenic | -0.002 | Destabilizing | 0.388 | N | 0.397 | neutral | None | None | None | None | N |
| R/E | 0.3862 | ambiguous | 0.3801 | ambiguous | 0.171 | Stabilizing | 0.116 | N | 0.393 | neutral | None | None | None | None | N |
| R/F | 0.6779 | likely_pathogenic | 0.686 | pathogenic | -0.389 | Destabilizing | 0.69 | D | 0.413 | neutral | None | None | None | None | N |
| R/G | 0.3814 | ambiguous | 0.4026 | ambiguous | -1.242 | Destabilizing | 0.324 | N | 0.377 | neutral | N | 0.497778243 | None | None | N |
| R/H | 0.1545 | likely_benign | 0.1619 | benign | -1.389 | Destabilizing | 0.818 | D | 0.447 | neutral | None | None | None | None | N |
| R/I | 0.2724 | likely_benign | 0.2862 | benign | 0.111 | Stabilizing | 0.001 | N | 0.287 | neutral | N | 0.489505476 | None | None | N |
| R/K | 0.1217 | likely_benign | 0.1238 | benign | -0.781 | Destabilizing | None | N | 0.106 | neutral | N | 0.391264066 | None | None | N |
| R/L | 0.2755 | likely_benign | 0.2893 | benign | 0.111 | Stabilizing | 0.043 | N | 0.363 | neutral | None | None | None | None | N |
| R/M | 0.2794 | likely_benign | 0.2867 | benign | -0.403 | Destabilizing | 0.69 | D | 0.423 | neutral | None | None | None | None | N |
| R/N | 0.604 | likely_pathogenic | 0.623 | pathogenic | -0.429 | Destabilizing | 0.388 | N | 0.419 | neutral | None | None | None | None | N |
| R/P | 0.6587 | likely_pathogenic | 0.6467 | pathogenic | -0.2 | Destabilizing | 0.818 | D | 0.381 | neutral | None | None | None | None | N |
| R/Q | 0.1076 | likely_benign | 0.111 | benign | -0.448 | Destabilizing | 0.241 | N | 0.447 | neutral | None | None | None | None | N |
| R/S | 0.5081 | ambiguous | 0.513 | ambiguous | -1.225 | Destabilizing | 0.193 | N | 0.374 | neutral | N | 0.444386475 | None | None | N |
| R/T | 0.2426 | likely_benign | 0.2453 | benign | -0.845 | Destabilizing | 0.324 | N | 0.372 | neutral | N | 0.414583643 | None | None | N |
| R/V | 0.3561 | ambiguous | 0.3492 | ambiguous | -0.2 | Destabilizing | 0.098 | N | 0.392 | neutral | None | None | None | None | N |
| R/W | 0.3152 | likely_benign | 0.3107 | benign | 0.019 | Stabilizing | 0.981 | D | 0.471 | neutral | None | None | None | None | N |
| R/Y | 0.483 | ambiguous | 0.4868 | ambiguous | 0.257 | Stabilizing | 0.818 | D | 0.405 | 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.