Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22310 | 67153;67154;67155 | chr2:178580451;178580450;178580449 | chr2:179445178;179445177;179445176 |
| N2AB | 20669 | 62230;62231;62232 | chr2:178580451;178580450;178580449 | chr2:179445178;179445177;179445176 |
| N2A | 19742 | 59449;59450;59451 | chr2:178580451;178580450;178580449 | chr2:179445178;179445177;179445176 |
| N2B | 13245 | 39958;39959;39960 | chr2:178580451;178580450;178580449 | chr2:179445178;179445177;179445176 |
| Novex-1 | 13370 | 40333;40334;40335 | chr2:178580451;178580450;178580449 | chr2:179445178;179445177;179445176 |
| Novex-2 | 13437 | 40534;40535;40536 | chr2:178580451;178580450;178580449 | chr2:179445178;179445177;179445176 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1315282961  |
-1.029 | 0.011 | N | 0.237 | 0.257 | 0.466571191598 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/L | rs1315282961 |
-1.029 | 0.011 | N | 0.237 | 0.257 | 0.466571191598 | 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 |
| I/L | rs1315282961 |
-1.029 | 0.011 | N | 0.237 | 0.257 | 0.466571191598 | gnomAD-4.0.0 | 6.57549E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47093E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.797 | likely_pathogenic | 0.8482 | pathogenic | -1.826 | Destabilizing | 0.916 | D | 0.455 | neutral | None | None | None | None | N |
| I/C | 0.8499 | likely_pathogenic | 0.8831 | pathogenic | -1.154 | Destabilizing | 0.999 | D | 0.621 | neutral | None | None | None | None | N |
| I/D | 0.9546 | likely_pathogenic | 0.9691 | pathogenic | -1.272 | Destabilizing | 0.996 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/E | 0.8502 | likely_pathogenic | 0.8904 | pathogenic | -1.185 | Destabilizing | 0.987 | D | 0.735 | prob.delet. | None | None | None | None | N |
| I/F | 0.3373 | likely_benign | 0.4049 | ambiguous | -1.115 | Destabilizing | 0.975 | D | 0.573 | neutral | None | None | None | None | N |
| I/G | 0.9368 | likely_pathogenic | 0.9581 | pathogenic | -2.226 | Highly Destabilizing | 0.987 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/H | 0.8784 | likely_pathogenic | 0.9108 | pathogenic | -1.31 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| I/K | 0.7675 | likely_pathogenic | 0.818 | pathogenic | -1.283 | Destabilizing | 0.983 | D | 0.732 | prob.delet. | N | 0.509778655 | None | None | N |
| I/L | 0.246 | likely_benign | 0.2813 | benign | -0.76 | Destabilizing | 0.011 | N | 0.237 | neutral | N | 0.484580374 | None | None | N |
| I/M | 0.2079 | likely_benign | 0.234 | benign | -0.665 | Destabilizing | 0.967 | D | 0.568 | neutral | N | 0.498849968 | None | None | N |
| I/N | 0.7282 | likely_pathogenic | 0.7953 | pathogenic | -1.292 | Destabilizing | 0.996 | D | 0.747 | deleterious | None | None | None | None | N |
| I/P | 0.9497 | likely_pathogenic | 0.9598 | pathogenic | -1.087 | Destabilizing | 0.996 | D | 0.747 | deleterious | None | None | None | None | N |
| I/Q | 0.7781 | likely_pathogenic | 0.8258 | pathogenic | -1.338 | Destabilizing | 0.996 | D | 0.747 | deleterious | None | None | None | None | N |
| I/R | 0.6958 | likely_pathogenic | 0.7585 | pathogenic | -0.783 | Destabilizing | 0.983 | D | 0.743 | deleterious | D | 0.528136399 | None | None | N |
| I/S | 0.7477 | likely_pathogenic | 0.8071 | pathogenic | -1.968 | Destabilizing | 0.987 | D | 0.645 | neutral | None | None | None | None | N |
| I/T | 0.6517 | likely_pathogenic | 0.7039 | pathogenic | -1.742 | Destabilizing | 0.967 | D | 0.577 | neutral | N | 0.502016747 | None | None | N |
| I/V | 0.1196 | likely_benign | 0.1333 | benign | -1.087 | Destabilizing | 0.426 | N | 0.432 | neutral | D | 0.522685048 | None | None | N |
| I/W | 0.875 | likely_pathogenic | 0.8994 | pathogenic | -1.245 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7428 | likely_pathogenic | 0.7991 | pathogenic | -0.999 | Destabilizing | 0.987 | D | 0.635 | 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.