Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1732 | 5419;5420;5421 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
| N2AB | 1732 | 5419;5420;5421 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
| N2A | 1732 | 5419;5420;5421 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
| N2B | 1686 | 5281;5282;5283 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
| Novex-1 | 1686 | 5281;5282;5283 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
| Novex-2 | 1686 | 5281;5282;5283 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
| Novex-3 | 1732 | 5419;5420;5421 | chr2:178776670;178776669;178776668 | chr2:179641397;179641396;179641395 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs1375104988  |
-0.127 | 1.0 | D | 0.749 | 0.742 | 0.606545613963 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1375104988 |
-0.127 | 1.0 | D | 0.749 | 0.742 | 0.606545613963 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1375104988 |
-0.127 | 1.0 | D | 0.749 | 0.742 | 0.606545613963 | gnomAD-4.0.0 | 6.57082E-06 | None | None | None | None | I | None | 2.41231E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6118 | likely_pathogenic | 0.6505 | pathogenic | -0.326 | Destabilizing | 1.0 | D | 0.744 | deleterious | D | 0.670233093 | None | None | I |
| P/C | 0.9905 | likely_pathogenic | 0.9901 | pathogenic | -0.753 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| P/D | 0.96 | likely_pathogenic | 0.9657 | pathogenic | -0.406 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | I |
| P/E | 0.8881 | likely_pathogenic | 0.9009 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| P/F | 0.9918 | likely_pathogenic | 0.9923 | pathogenic | -0.742 | Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | I |
| P/G | 0.9342 | likely_pathogenic | 0.9397 | pathogenic | -0.379 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| P/H | 0.879 | likely_pathogenic | 0.8829 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| P/I | 0.9603 | likely_pathogenic | 0.9651 | pathogenic | -0.33 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| P/K | 0.9156 | likely_pathogenic | 0.9222 | pathogenic | -0.392 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| P/L | 0.8304 | likely_pathogenic | 0.8564 | pathogenic | -0.33 | Destabilizing | 1.0 | D | 0.771 | deleterious | D | 0.730550229 | None | None | I |
| P/M | 0.9573 | likely_pathogenic | 0.9604 | pathogenic | -0.52 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | I |
| P/N | 0.9447 | likely_pathogenic | 0.9506 | pathogenic | -0.175 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| P/Q | 0.7953 | likely_pathogenic | 0.8101 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.77 | deleterious | D | 0.739417302 | None | None | I |
| P/R | 0.8344 | likely_pathogenic | 0.8442 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.789 | deleterious | D | 0.767187429 | None | None | I |
| P/S | 0.7571 | likely_pathogenic | 0.7808 | pathogenic | -0.464 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.609298601 | None | None | I |
| P/T | 0.7676 | likely_pathogenic | 0.7956 | pathogenic | -0.5 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.730086538 | None | None | I |
| P/V | 0.9145 | likely_pathogenic | 0.9228 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| P/W | 0.9961 | likely_pathogenic | 0.9965 | pathogenic | -0.804 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| P/Y | 0.9866 | likely_pathogenic | 0.9873 | pathogenic | -0.524 | Destabilizing | 1.0 | D | 0.817 | 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.