Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23388 | 70387;70388;70389 | chr2:178575970;178575969;178575968 | chr2:179440697;179440696;179440695 |
| N2AB | 21747 | 65464;65465;65466 | chr2:178575970;178575969;178575968 | chr2:179440697;179440696;179440695 |
| N2A | 20820 | 62683;62684;62685 | chr2:178575970;178575969;178575968 | chr2:179440697;179440696;179440695 |
| N2B | 14323 | 43192;43193;43194 | chr2:178575970;178575969;178575968 | chr2:179440697;179440696;179440695 |
| Novex-1 | 14448 | 43567;43568;43569 | chr2:178575970;178575969;178575968 | chr2:179440697;179440696;179440695 |
| Novex-2 | 14515 | 43768;43769;43770 | chr2:178575970;178575969;178575968 | chr2:179440697;179440696;179440695 |
| 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 | rs781540455  |
-0.553 | 1.0 | N | 0.632 | 0.402 | 0.484109215787 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.81E-06 | 0 |
| R/G | rs781540455 |
-0.553 | 1.0 | N | 0.632 | 0.402 | 0.484109215787 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 1.47E-05 | 0 | 0 |
| R/G | rs781540455 |
-0.553 | 1.0 | N | 0.632 | 0.402 | 0.484109215787 | gnomAD-4.0.0 | 6.20683E-06 | None | None | None | None | N | None | 0 | 1.66867E-05 | None | 0 | 0 | None | 0 | 1.64962E-04 | 5.94327E-06 | 0 | 1.60344E-05 |
| R/Q | rs55853138 |
0.163 | 1.0 | N | 0.675 | 0.338 | None | gnomAD-2.1.1 | 6.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.13E-05 | None | 0 | None | 4.02E-05 | 1.17186E-04 | 0 |
| R/Q | rs55853138 |
0.163 | 1.0 | N | 0.675 | 0.338 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 1.47098E-04 | 0 | 0 |
| R/Q | rs55853138 |
0.163 | 1.0 | N | 0.675 | 0.338 | None | gnomAD-4.0.0 | 6.33061E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23294E-05 | None | 3.13156E-05 | 0 | 8.1505E-05 | 2.19785E-05 | 1.60323E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8199 | likely_pathogenic | 0.8753 | pathogenic | -0.463 | Destabilizing | 0.999 | D | 0.561 | neutral | None | None | None | None | N |
| R/C | 0.5134 | ambiguous | 0.6147 | pathogenic | -0.438 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/D | 0.9018 | likely_pathogenic | 0.9261 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| R/E | 0.7484 | likely_pathogenic | 0.8013 | pathogenic | 0.158 | Stabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| R/F | 0.895 | likely_pathogenic | 0.9271 | pathogenic | -0.364 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | N |
| R/G | 0.7553 | likely_pathogenic | 0.8354 | pathogenic | -0.77 | Destabilizing | 1.0 | D | 0.632 | neutral | N | 0.485818373 | None | None | N |
| R/H | 0.2451 | likely_benign | 0.297 | benign | -1.284 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/I | 0.6331 | likely_pathogenic | 0.7114 | pathogenic | 0.354 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/K | 0.2307 | likely_benign | 0.2904 | benign | -0.392 | Destabilizing | 0.998 | D | 0.507 | neutral | None | None | None | None | N |
| R/L | 0.6158 | likely_pathogenic | 0.7056 | pathogenic | 0.354 | Stabilizing | 1.0 | D | 0.632 | neutral | N | 0.479741987 | None | None | N |
| R/M | 0.69 | likely_pathogenic | 0.7835 | pathogenic | -0.095 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| R/N | 0.8868 | likely_pathogenic | 0.9203 | pathogenic | -0.049 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| R/P | 0.9487 | likely_pathogenic | 0.9693 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.627 | neutral | N | 0.498442126 | None | None | N |
| R/Q | 0.2342 | likely_benign | 0.285 | benign | -0.124 | Destabilizing | 1.0 | D | 0.675 | neutral | N | 0.473501016 | None | None | N |
| R/S | 0.887 | likely_pathogenic | 0.9268 | pathogenic | -0.673 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| R/T | 0.6539 | likely_pathogenic | 0.7467 | pathogenic | -0.353 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| R/V | 0.7361 | likely_pathogenic | 0.8034 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/W | 0.4443 | ambiguous | 0.5259 | ambiguous | -0.162 | Destabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| R/Y | 0.7234 | likely_pathogenic | 0.7849 | pathogenic | 0.18 | Stabilizing | 1.0 | D | 0.657 | 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.