Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28491 | 85696;85697;85698 | chr2:178560661;178560660;178560659 | chr2:179425388;179425387;179425386 |
| N2AB | 26850 | 80773;80774;80775 | chr2:178560661;178560660;178560659 | chr2:179425388;179425387;179425386 |
| N2A | 25923 | 77992;77993;77994 | chr2:178560661;178560660;178560659 | chr2:179425388;179425387;179425386 |
| N2B | 19426 | 58501;58502;58503 | chr2:178560661;178560660;178560659 | chr2:179425388;179425387;179425386 |
| Novex-1 | 19551 | 58876;58877;58878 | chr2:178560661;178560660;178560659 | chr2:179425388;179425387;179425386 |
| Novex-2 | 19618 | 59077;59078;59079 | chr2:178560661;178560660;178560659 | chr2:179425388;179425387;179425386 |
| 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/C | rs746090724  |
-1.83 | 1.0 | N | 0.761 | 0.412 | 0.635445006688 | gnomAD-2.1.1 | 5.37E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 4.57666E-04 | None | 0 | 0 | 0 |
| R/C | rs746090724 |
-1.83 | 1.0 | N | 0.761 | 0.412 | 0.635445006688 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 1.31182E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/C | rs746090724 |
-1.83 | 1.0 | N | 0.761 | 0.412 | 0.635445006688 | gnomAD-4.0.0 | 2.16931E-05 | None | None | None | None | N | None | 0 | 5.00367E-05 | None | 0 | 0 | None | 0 | 0 | 2.54291E-06 | 3.18408E-04 | 0 |
| R/H | rs373129706 |
-2.483 | 0.997 | D | 0.584 | 0.524 | None | gnomAD-2.1.1 | 1.10946E-04 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 1.23571E-03 | None | 6.54E-05 | None | 0 | 3.14E-05 | 0 |
| R/H | rs373129706 |
-2.483 | 0.997 | D | 0.584 | 0.524 | None | gnomAD-3.1.2 | 7.23E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 1.5444E-03 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/H | rs373129706 |
-2.483 | 0.997 | D | 0.584 | 0.524 | None | gnomAD-4.0.0 | 5.82597E-05 | None | None | None | None | N | None | 2.67008E-05 | 0 | None | 0 | 8.70303E-04 | None | 0 | 0 | 3.56E-05 | 9.88207E-05 | 3.20277E-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 | 0.8952 | likely_pathogenic | 0.9424 | pathogenic | -2.062 | Highly Destabilizing | 0.916 | D | 0.552 | neutral | None | None | None | None | N |
| R/C | 0.3034 | likely_benign | 0.361 | ambiguous | -1.889 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.475980822 | None | None | N |
| R/D | 0.9881 | likely_pathogenic | 0.9944 | pathogenic | -0.78 | Destabilizing | 0.975 | D | 0.729 | prob.delet. | None | None | None | None | N |
| R/E | 0.8335 | likely_pathogenic | 0.9101 | pathogenic | -0.571 | Destabilizing | 0.845 | D | 0.447 | neutral | None | None | None | None | N |
| R/F | 0.9461 | likely_pathogenic | 0.9731 | pathogenic | -1.32 | Destabilizing | 0.996 | D | 0.796 | deleterious | None | None | None | None | N |
| R/G | 0.8023 | likely_pathogenic | 0.8808 | pathogenic | -2.4 | Highly Destabilizing | 0.954 | D | 0.679 | prob.neutral | N | 0.518025455 | None | None | N |
| R/H | 0.3997 | ambiguous | 0.4472 | ambiguous | -2.157 | Highly Destabilizing | 0.997 | D | 0.584 | neutral | D | 0.522317869 | None | None | N |
| R/I | 0.8395 | likely_pathogenic | 0.9222 | pathogenic | -1.08 | Destabilizing | 0.987 | D | 0.801 | deleterious | None | None | None | None | N |
| R/K | 0.2069 | likely_benign | 0.3106 | benign | -1.295 | Destabilizing | 0.693 | D | 0.4 | neutral | None | None | None | None | N |
| R/L | 0.7349 | likely_pathogenic | 0.8305 | pathogenic | -1.08 | Destabilizing | 0.954 | D | 0.679 | prob.neutral | N | 0.499325316 | None | None | N |
| R/M | 0.6436 | likely_pathogenic | 0.8117 | pathogenic | -1.551 | Destabilizing | 0.997 | D | 0.743 | deleterious | None | None | None | None | N |
| R/N | 0.96 | likely_pathogenic | 0.979 | pathogenic | -1.158 | Destabilizing | 0.975 | D | 0.578 | neutral | None | None | None | None | N |
| R/P | 0.995 | likely_pathogenic | 0.9976 | pathogenic | -1.396 | Destabilizing | 0.993 | D | 0.802 | deleterious | D | 0.533420685 | None | None | N |
| R/Q | 0.2069 | likely_benign | 0.2584 | benign | -1.116 | Destabilizing | 0.253 | N | 0.283 | neutral | None | None | None | None | N |
| R/S | 0.9479 | likely_pathogenic | 0.9747 | pathogenic | -2.156 | Highly Destabilizing | 0.954 | D | 0.656 | neutral | N | 0.493093891 | None | None | N |
| R/T | 0.8549 | likely_pathogenic | 0.9386 | pathogenic | -1.739 | Destabilizing | 0.975 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/V | 0.8655 | likely_pathogenic | 0.9262 | pathogenic | -1.396 | Destabilizing | 0.975 | D | 0.795 | deleterious | None | None | None | None | N |
| R/W | 0.5591 | ambiguous | 0.7193 | pathogenic | -0.764 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| R/Y | 0.8244 | likely_pathogenic | 0.8948 | pathogenic | -0.641 | Destabilizing | 0.996 | D | 0.807 | deleterious | 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.