Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24455 | 73588;73589;73590 | chr2:178572769;178572768;178572767 | chr2:179437496;179437495;179437494 |
| N2AB | 22814 | 68665;68666;68667 | chr2:178572769;178572768;178572767 | chr2:179437496;179437495;179437494 |
| N2A | 21887 | 65884;65885;65886 | chr2:178572769;178572768;178572767 | chr2:179437496;179437495;179437494 |
| N2B | 15390 | 46393;46394;46395 | chr2:178572769;178572768;178572767 | chr2:179437496;179437495;179437494 |
| Novex-1 | 15515 | 46768;46769;46770 | chr2:178572769;178572768;178572767 | chr2:179437496;179437495;179437494 |
| Novex-2 | 15582 | 46969;46970;46971 | chr2:178572769;178572768;178572767 | chr2:179437496;179437495;179437494 |
| 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/G | rs777909869  |
-0.238 | 1.0 | D | 0.657 | 0.492 | 0.72859088309 | 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 |
| R/G | rs777909869 |
-0.238 | 1.0 | D | 0.657 | 0.492 | 0.72859088309 | gnomAD-4.0.0 | 1.59185E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85943E-06 | 0 | 0 |
| R/K | None | None | 0.997 | N | 0.5 | 0.321 | 0.351180957027 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.9648 | likely_pathogenic | 0.9607 | pathogenic | 0.105 | Stabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | I |
| R/C | 0.521 | ambiguous | 0.5048 | ambiguous | -0.026 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| R/D | 0.9901 | likely_pathogenic | 0.989 | pathogenic | -0.162 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| R/E | 0.9284 | likely_pathogenic | 0.923 | pathogenic | -0.101 | Destabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | I |
| R/F | 0.8881 | likely_pathogenic | 0.8834 | pathogenic | -0.105 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| R/G | 0.954 | likely_pathogenic | 0.9491 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.657 | neutral | D | 0.523484682 | None | None | I |
| R/H | 0.3063 | likely_benign | 0.2876 | benign | -0.623 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| R/I | 0.6641 | likely_pathogenic | 0.6515 | pathogenic | 0.565 | Stabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| R/K | 0.2519 | likely_benign | 0.2335 | benign | 0.015 | Stabilizing | 0.997 | D | 0.5 | neutral | N | 0.485476241 | None | None | I |
| R/L | 0.7616 | likely_pathogenic | 0.7486 | pathogenic | 0.565 | Stabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | I |
| R/M | 0.8053 | likely_pathogenic | 0.7855 | pathogenic | 0.094 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.501114466 | None | None | I |
| R/N | 0.9576 | likely_pathogenic | 0.9529 | pathogenic | 0.227 | Stabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| R/P | 0.9966 | likely_pathogenic | 0.9962 | pathogenic | 0.432 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/Q | 0.3481 | ambiguous | 0.3293 | benign | 0.151 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/S | 0.9626 | likely_pathogenic | 0.9565 | pathogenic | -0.031 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.483348925 | None | None | I |
| R/T | 0.9051 | likely_pathogenic | 0.8939 | pathogenic | 0.157 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | N | 0.498072592 | None | None | I |
| R/V | 0.8035 | likely_pathogenic | 0.7912 | pathogenic | 0.432 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/W | 0.5126 | ambiguous | 0.4972 | ambiguous | -0.21 | Destabilizing | 1.0 | D | 0.776 | deleterious | D | 0.523991661 | None | None | I |
| R/Y | 0.7292 | likely_pathogenic | 0.7174 | pathogenic | 0.198 | Stabilizing | 1.0 | D | 0.747 | deleterious | 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.