Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23315 | 70168;70169;70170 | chr2:178576189;178576188;178576187 | chr2:179440916;179440915;179440914 |
| N2AB | 21674 | 65245;65246;65247 | chr2:178576189;178576188;178576187 | chr2:179440916;179440915;179440914 |
| N2A | 20747 | 62464;62465;62466 | chr2:178576189;178576188;178576187 | chr2:179440916;179440915;179440914 |
| N2B | 14250 | 42973;42974;42975 | chr2:178576189;178576188;178576187 | chr2:179440916;179440915;179440914 |
| Novex-1 | 14375 | 43348;43349;43350 | chr2:178576189;178576188;178576187 | chr2:179440916;179440915;179440914 |
| Novex-2 | 14442 | 43549;43550;43551 | chr2:178576189;178576188;178576187 | chr2:179440916;179440915;179440914 |
| 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 | rs756974395  |
-1.105 | 0.997 | N | 0.687 | 0.414 | 0.523650220922 | gnomAD-2.1.1 | 6.38E-05 | None | None | None | None | N | None | 2.29568E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs756974395 |
-1.105 | 0.997 | N | 0.687 | 0.414 | 0.523650220922 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs756974395 |
-1.105 | 0.997 | N | 0.687 | 0.414 | 0.523650220922 | gnomAD-4.0.0 | 3.84767E-06 | None | None | None | None | N | None | 3.38524E-05 | 0 | None | 0 | 2.43108E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | None | 1.0 | N | 0.75 | 0.585 | 0.454518106513 | gnomAD-4.0.0 | 1.59308E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77932E-05 | None | 0 | 0 | 0 | 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 | 0.8749 | likely_pathogenic | 0.9059 | pathogenic | -1.661 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/C | 0.2467 | likely_benign | 0.251 | benign | -1.621 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/D | 0.987 | likely_pathogenic | 0.9877 | pathogenic | -0.76 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| R/E | 0.8512 | likely_pathogenic | 0.8723 | pathogenic | -0.544 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/F | 0.9269 | likely_pathogenic | 0.9399 | pathogenic | -0.847 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| R/G | 0.8797 | likely_pathogenic | 0.8982 | pathogenic | -2.021 | Highly Destabilizing | 1.0 | D | 0.766 | deleterious | D | 0.546907039 | None | None | N |
| R/H | 0.2151 | likely_benign | 0.2137 | benign | -1.864 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/I | 0.6876 | likely_pathogenic | 0.7492 | pathogenic | -0.626 | Destabilizing | 1.0 | D | 0.848 | deleterious | D | 0.524194428 | None | None | N |
| R/K | 0.2373 | likely_benign | 0.323 | benign | -1.138 | Destabilizing | 0.997 | D | 0.687 | prob.neutral | N | 0.500668442 | None | None | N |
| R/L | 0.672 | likely_pathogenic | 0.7236 | pathogenic | -0.626 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| R/M | 0.7356 | likely_pathogenic | 0.8089 | pathogenic | -1.17 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| R/N | 0.9266 | likely_pathogenic | 0.9302 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/P | 0.9977 | likely_pathogenic | 0.9982 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| R/Q | 0.174 | likely_benign | 0.1872 | benign | -0.973 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| R/S | 0.9036 | likely_pathogenic | 0.9176 | pathogenic | -1.971 | Destabilizing | 1.0 | D | 0.75 | deleterious | N | 0.517113629 | None | None | N |
| R/T | 0.8098 | likely_pathogenic | 0.8596 | pathogenic | -1.541 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.493515645 | None | None | N |
| R/V | 0.7452 | likely_pathogenic | 0.7973 | pathogenic | -0.958 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| R/W | 0.5974 | likely_pathogenic | 0.5965 | pathogenic | -0.402 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| R/Y | 0.8152 | likely_pathogenic | 0.8328 | pathogenic | -0.228 | Destabilizing | 1.0 | D | 0.855 | deleterious | 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.