Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22512 | 67759;67760;67761 | chr2:178579663;178579662;178579661 | chr2:179444390;179444389;179444388 |
| N2AB | 20871 | 62836;62837;62838 | chr2:178579663;178579662;178579661 | chr2:179444390;179444389;179444388 |
| N2A | 19944 | 60055;60056;60057 | chr2:178579663;178579662;178579661 | chr2:179444390;179444389;179444388 |
| N2B | 13447 | 40564;40565;40566 | chr2:178579663;178579662;178579661 | chr2:179444390;179444389;179444388 |
| Novex-1 | 13572 | 40939;40940;40941 | chr2:178579663;178579662;178579661 | chr2:179444390;179444389;179444388 |
| Novex-2 | 13639 | 41140;41141;41142 | chr2:178579663;178579662;178579661 | chr2:179444390;179444389;179444388 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs760531418  |
None | 0.039 | N | 0.225 | 0.069 | 0.130388298395 | gnomAD-4.0.0 | 1.08029E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18125E-05 | 0 | 0 |
| D/G | None | None | 0.928 | N | 0.719 | 0.459 | 0.297031009988 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/Y | rs786205540 |
None | 0.999 | N | 0.749 | 0.371 | 0.638151879823 | gnomAD-4.0.0 | 3.18433E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.82859E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1716 | likely_benign | 0.169 | benign | -0.073 | Destabilizing | 0.865 | D | 0.684 | prob.neutral | N | 0.47368987 | None | None | N |
| D/C | 0.5903 | likely_pathogenic | 0.5811 | pathogenic | -0.046 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | N |
| D/E | 0.1526 | likely_benign | 0.1522 | benign | -0.268 | Destabilizing | 0.039 | N | 0.225 | neutral | N | 0.49591416 | None | None | N |
| D/F | 0.4921 | ambiguous | 0.5255 | ambiguous | -0.146 | Destabilizing | 0.999 | D | 0.749 | deleterious | None | None | None | None | N |
| D/G | 0.1058 | likely_benign | 0.1009 | benign | -0.193 | Destabilizing | 0.928 | D | 0.719 | prob.delet. | N | 0.409289679 | None | None | N |
| D/H | 0.271 | likely_benign | 0.2571 | benign | 0.373 | Stabilizing | 0.997 | D | 0.718 | prob.delet. | N | 0.481932304 | None | None | N |
| D/I | 0.3402 | ambiguous | 0.3414 | ambiguous | 0.176 | Stabilizing | 0.992 | D | 0.757 | deleterious | None | None | None | None | N |
| D/K | 0.3793 | ambiguous | 0.3602 | ambiguous | 0.449 | Stabilizing | 0.968 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/L | 0.3448 | ambiguous | 0.3456 | ambiguous | 0.176 | Stabilizing | 0.983 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/M | 0.5534 | ambiguous | 0.5565 | ambiguous | 0.092 | Stabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| D/N | 0.0916 | likely_benign | 0.0889 | benign | 0.215 | Stabilizing | 0.978 | D | 0.761 | deleterious | N | 0.464743104 | None | None | N |
| D/P | 0.7062 | likely_pathogenic | 0.6951 | pathogenic | 0.112 | Stabilizing | 0.992 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/Q | 0.3196 | likely_benign | 0.3115 | benign | 0.215 | Stabilizing | 0.968 | D | 0.753 | deleterious | None | None | None | None | N |
| D/R | 0.4241 | ambiguous | 0.4132 | ambiguous | 0.647 | Stabilizing | 0.983 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/S | 0.138 | likely_benign | 0.1326 | benign | 0.116 | Stabilizing | 0.895 | D | 0.673 | neutral | None | None | None | None | N |
| D/T | 0.2457 | likely_benign | 0.2395 | benign | 0.214 | Stabilizing | 0.983 | D | 0.737 | prob.delet. | None | None | None | None | N |
| D/V | 0.1987 | likely_benign | 0.1989 | benign | 0.112 | Stabilizing | 0.978 | D | 0.728 | prob.delet. | N | 0.497581023 | None | None | N |
| D/W | 0.8294 | likely_pathogenic | 0.8414 | pathogenic | -0.083 | Destabilizing | 0.999 | D | 0.775 | deleterious | None | None | None | None | N |
| D/Y | 0.1809 | likely_benign | 0.1819 | benign | 0.083 | Stabilizing | 0.999 | D | 0.749 | deleterious | N | 0.490579584 | 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.