Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17635 | 53128;53129;53130 | chr2:178607884;178607883;178607882 | chr2:179472611;179472610;179472609 |
| N2AB | 15994 | 48205;48206;48207 | chr2:178607884;178607883;178607882 | chr2:179472611;179472610;179472609 |
| N2A | 15067 | 45424;45425;45426 | chr2:178607884;178607883;178607882 | chr2:179472611;179472610;179472609 |
| N2B | 8570 | 25933;25934;25935 | chr2:178607884;178607883;178607882 | chr2:179472611;179472610;179472609 |
| Novex-1 | 8695 | 26308;26309;26310 | chr2:178607884;178607883;178607882 | chr2:179472611;179472610;179472609 |
| Novex-2 | 8762 | 26509;26510;26511 | chr2:178607884;178607883;178607882 | chr2:179472611;179472610;179472609 |
| 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/L | rs773522736  |
0.423 | 1.0 | N | 0.595 | 0.357 | 0.481172606772 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| R/L | rs773522736 |
0.423 | 1.0 | N | 0.595 | 0.357 | 0.481172606772 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs773522736 |
-0.056 | 1.0 | N | 0.703 | 0.316 | 0.243398259712 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs773522736 |
-0.056 | 1.0 | N | 0.703 | 0.316 | 0.243398259712 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs773522736 |
-0.056 | 1.0 | N | 0.703 | 0.316 | 0.243398259712 | gnomAD-4.0.0 | 8.05993E-06 | None | None | None | None | N | None | 4.00716E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.63156E-06 | 0 | 1.60236E-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 | 0.6102 | likely_pathogenic | 0.5627 | ambiguous | -0.016 | Destabilizing | 0.999 | D | 0.59 | neutral | None | None | None | None | N |
| R/C | 0.3333 | likely_benign | 0.3137 | benign | -0.394 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/D | 0.8584 | likely_pathogenic | 0.8295 | pathogenic | -0.236 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/E | 0.541 | ambiguous | 0.4939 | ambiguous | -0.15 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | N |
| R/F | 0.767 | likely_pathogenic | 0.7121 | pathogenic | -0.274 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | N |
| R/G | 0.5254 | ambiguous | 0.4486 | ambiguous | -0.206 | Destabilizing | 1.0 | D | 0.595 | neutral | N | 0.472017576 | None | None | N |
| R/H | 0.2239 | likely_benign | 0.1972 | benign | -0.865 | Destabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| R/I | 0.3868 | ambiguous | 0.3665 | ambiguous | 0.45 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/K | 0.1888 | likely_benign | 0.1705 | benign | -0.137 | Destabilizing | 0.998 | D | 0.485 | neutral | None | None | None | None | N |
| R/L | 0.3849 | ambiguous | 0.3554 | ambiguous | 0.45 | Stabilizing | 1.0 | D | 0.595 | neutral | N | 0.477096326 | None | None | N |
| R/M | 0.411 | ambiguous | 0.3775 | ambiguous | -0.162 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/N | 0.8121 | likely_pathogenic | 0.774 | pathogenic | -0.193 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/P | 0.7609 | likely_pathogenic | 0.7224 | pathogenic | 0.314 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.47201858 | None | None | N |
| R/Q | 0.1719 | likely_benign | 0.1489 | benign | -0.152 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.466244614 | None | None | N |
| R/S | 0.7236 | likely_pathogenic | 0.6653 | pathogenic | -0.425 | Destabilizing | 1.0 | D | 0.65 | neutral | None | None | None | None | N |
| R/T | 0.3425 | ambiguous | 0.301 | benign | -0.196 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | N |
| R/V | 0.4853 | ambiguous | 0.4542 | ambiguous | 0.314 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/W | 0.2747 | likely_benign | 0.2375 | benign | -0.428 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| R/Y | 0.64 | likely_pathogenic | 0.5908 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | 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.