Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2276 | 7051;7052;7053 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
| N2AB | 2276 | 7051;7052;7053 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
| N2A | 2276 | 7051;7052;7053 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
| N2B | 2230 | 6913;6914;6915 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
| Novex-1 | 2230 | 6913;6914;6915 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
| Novex-2 | 2230 | 6913;6914;6915 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
| Novex-3 | 2276 | 7051;7052;7053 | chr2:178774438;178774437;178774436 | chr2:179639165;179639164;179639163 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs780309167  |
-0.663 | 0.901 | N | 0.455 | 0.188 | 0.453588565359 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/M | rs780309167 |
-0.663 | 0.901 | N | 0.455 | 0.188 | 0.453588565359 | gnomAD-4.0.0 | 4.77617E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57138E-06 | 0 | 0 |
| I/T | None | None | 0.722 | N | 0.525 | 0.308 | 0.633325178372 | gnomAD-4.0.0 | 2.40078E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62515E-06 | 0 | 0 |
| I/V | rs794729578 |
-1.029 | 0.003 | N | 0.131 | 0.089 | 0.378322506985 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.46E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs794729578 |
-1.029 | 0.003 | N | 0.131 | 0.089 | 0.378322506985 | gnomAD-4.0.0 | 1.36882E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52156E-05 | None | 0 | 0 | 8.99399E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2255 | likely_benign | 0.2102 | benign | -1.493 | Destabilizing | 0.415 | N | 0.576 | neutral | None | None | None | None | N |
| I/C | 0.6845 | likely_pathogenic | 0.6815 | pathogenic | -0.856 | Destabilizing | 0.996 | D | 0.527 | neutral | None | None | None | None | N |
| I/D | 0.7716 | likely_pathogenic | 0.7446 | pathogenic | -1.035 | Destabilizing | 0.987 | D | 0.671 | neutral | None | None | None | None | N |
| I/E | 0.5384 | ambiguous | 0.5151 | ambiguous | -1.05 | Destabilizing | 0.961 | D | 0.654 | neutral | None | None | None | None | N |
| I/F | 0.2158 | likely_benign | 0.1987 | benign | -1.085 | Destabilizing | 0.858 | D | 0.443 | neutral | None | None | None | None | N |
| I/G | 0.6775 | likely_pathogenic | 0.6412 | pathogenic | -1.798 | Destabilizing | 0.961 | D | 0.647 | neutral | None | None | None | None | N |
| I/H | 0.6031 | likely_pathogenic | 0.5847 | pathogenic | -1.118 | Destabilizing | 0.996 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/K | 0.3374 | likely_benign | 0.3223 | benign | -1.096 | Destabilizing | 0.949 | D | 0.645 | neutral | N | 0.479651243 | None | None | N |
| I/L | 0.134 | likely_benign | 0.1286 | benign | -0.741 | Destabilizing | 0.003 | N | 0.127 | neutral | N | 0.366410906 | None | None | N |
| I/M | 0.0923 | likely_benign | 0.0893 | benign | -0.555 | Destabilizing | 0.901 | D | 0.455 | neutral | N | 0.489544662 | None | None | N |
| I/N | 0.3817 | ambiguous | 0.3509 | ambiguous | -0.858 | Destabilizing | 0.987 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/P | 0.9682 | likely_pathogenic | 0.9569 | pathogenic | -0.96 | Destabilizing | 0.987 | D | 0.671 | neutral | None | None | None | None | N |
| I/Q | 0.4205 | ambiguous | 0.407 | ambiguous | -1.043 | Destabilizing | 0.987 | D | 0.671 | neutral | None | None | None | None | N |
| I/R | 0.2831 | likely_benign | 0.2661 | benign | -0.514 | Destabilizing | 0.949 | D | 0.676 | prob.neutral | N | 0.490690572 | None | None | N |
| I/S | 0.2852 | likely_benign | 0.27 | benign | -1.402 | Destabilizing | 0.923 | D | 0.57 | neutral | None | None | None | None | N |
| I/T | 0.0968 | likely_benign | 0.0946 | benign | -1.305 | Destabilizing | 0.722 | D | 0.525 | neutral | N | 0.47438295 | None | None | N |
| I/V | 0.0687 | likely_benign | 0.069 | benign | -0.96 | Destabilizing | 0.003 | N | 0.131 | neutral | N | 0.373670374 | None | None | N |
| I/W | 0.8424 | likely_pathogenic | 0.8227 | pathogenic | -1.173 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/Y | 0.6343 | likely_pathogenic | 0.6105 | pathogenic | -0.949 | Destabilizing | 0.961 | D | 0.547 | 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.