Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19400 | 58423;58424;58425 | chr2:178594195;178594194;178594193 | chr2:179458922;179458921;179458920 |
| N2AB | 17759 | 53500;53501;53502 | chr2:178594195;178594194;178594193 | chr2:179458922;179458921;179458920 |
| N2A | 16832 | 50719;50720;50721 | chr2:178594195;178594194;178594193 | chr2:179458922;179458921;179458920 |
| N2B | 10335 | 31228;31229;31230 | chr2:178594195;178594194;178594193 | chr2:179458922;179458921;179458920 |
| Novex-1 | 10460 | 31603;31604;31605 | chr2:178594195;178594194;178594193 | chr2:179458922;179458921;179458920 |
| Novex-2 | 10527 | 31804;31805;31806 | chr2:178594195;178594194;178594193 | chr2:179458922;179458921;179458920 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.928 | N | 0.437 | 0.26 | 0.41958645093 | gnomAD-4.0.0 | 4.10641E-06 | None | None | None | None | I | None | 2.98864E-05 | 0 | None | 3.8279E-05 | 0 | None | 0 | 0 | 2.69876E-06 | 0 | 1.65706E-05 |
| V/G | rs774737543  |
-1.068 | 0.989 | N | 0.78 | 0.519 | 0.686624564747 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/G | rs774737543 |
-1.068 | 0.989 | N | 0.78 | 0.519 | 0.686624564747 | gnomAD-4.0.0 | 4.79081E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39752E-06 | 0 | 1.65706E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1378 | likely_benign | 0.1253 | benign | -1.03 | Destabilizing | 0.928 | D | 0.437 | neutral | N | 0.468521623 | None | None | I |
| V/C | 0.8178 | likely_pathogenic | 0.7978 | pathogenic | -0.789 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | I |
| V/D | 0.6563 | likely_pathogenic | 0.5798 | pathogenic | -0.666 | Destabilizing | 0.996 | D | 0.8 | deleterious | N | 0.476736111 | None | None | I |
| V/E | 0.3872 | ambiguous | 0.3238 | benign | -0.715 | Destabilizing | 0.997 | D | 0.749 | deleterious | None | None | None | None | I |
| V/F | 0.4029 | ambiguous | 0.3338 | benign | -0.827 | Destabilizing | 0.978 | D | 0.722 | prob.delet. | N | 0.483319477 | None | None | I |
| V/G | 0.378 | ambiguous | 0.3355 | benign | -1.277 | Destabilizing | 0.989 | D | 0.78 | deleterious | N | 0.495093856 | None | None | I |
| V/H | 0.8108 | likely_pathogenic | 0.7492 | pathogenic | -0.707 | Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | I |
| V/I | 0.1274 | likely_benign | 0.1152 | benign | -0.483 | Destabilizing | 0.039 | N | 0.297 | neutral | N | 0.452337979 | None | None | I |
| V/K | 0.5897 | likely_pathogenic | 0.5182 | ambiguous | -0.936 | Destabilizing | 0.992 | D | 0.755 | deleterious | None | None | None | None | I |
| V/L | 0.5272 | ambiguous | 0.4497 | ambiguous | -0.483 | Destabilizing | 0.476 | N | 0.452 | neutral | N | 0.505578502 | None | None | I |
| V/M | 0.3128 | likely_benign | 0.2651 | benign | -0.436 | Destabilizing | 0.983 | D | 0.69 | prob.neutral | None | None | None | None | I |
| V/N | 0.5037 | ambiguous | 0.4268 | ambiguous | -0.689 | Destabilizing | 0.997 | D | 0.804 | deleterious | None | None | None | None | I |
| V/P | 0.8178 | likely_pathogenic | 0.7424 | pathogenic | -0.629 | Destabilizing | 0.997 | D | 0.775 | deleterious | None | None | None | None | I |
| V/Q | 0.5138 | ambiguous | 0.4493 | ambiguous | -0.888 | Destabilizing | 0.997 | D | 0.775 | deleterious | None | None | None | None | I |
| V/R | 0.5364 | ambiguous | 0.4634 | ambiguous | -0.368 | Destabilizing | 0.997 | D | 0.802 | deleterious | None | None | None | None | I |
| V/S | 0.2478 | likely_benign | 0.2172 | benign | -1.168 | Destabilizing | 0.992 | D | 0.759 | deleterious | None | None | None | None | I |
| V/T | 0.2398 | likely_benign | 0.2143 | benign | -1.11 | Destabilizing | 0.944 | D | 0.655 | neutral | None | None | None | None | I |
| V/W | 0.9544 | likely_pathogenic | 0.9297 | pathogenic | -0.944 | Destabilizing | 0.999 | D | 0.801 | deleterious | None | None | None | None | I |
| V/Y | 0.8124 | likely_pathogenic | 0.7564 | pathogenic | -0.672 | Destabilizing | 0.992 | D | 0.733 | prob.delet. | 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.