Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24711 | 74356;74357;74358 | chr2:178572001;178572000;178571999 | chr2:179436728;179436727;179436726 |
| N2AB | 23070 | 69433;69434;69435 | chr2:178572001;178572000;178571999 | chr2:179436728;179436727;179436726 |
| N2A | 22143 | 66652;66653;66654 | chr2:178572001;178572000;178571999 | chr2:179436728;179436727;179436726 |
| N2B | 15646 | 47161;47162;47163 | chr2:178572001;178572000;178571999 | chr2:179436728;179436727;179436726 |
| Novex-1 | 15771 | 47536;47537;47538 | chr2:178572001;178572000;178571999 | chr2:179436728;179436727;179436726 |
| Novex-2 | 15838 | 47737;47738;47739 | chr2:178572001;178572000;178571999 | chr2:179436728;179436727;179436726 |
| 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 | rs1708361319  |
None | 0.001 | N | 0.364 | 0.166 | 0.0611884634855 | gnomAD-4.0.0 | 2.0533E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69884E-06 | 0 | 0 |
| D/V | rs765607630 |
0.351 | 0.909 | N | 0.729 | 0.503 | 0.575012909346 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| D/V | rs765607630 |
0.351 | 0.909 | N | 0.729 | 0.503 | 0.575012909346 | gnomAD-4.0.0 | 4.79102E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11651E-05 | 0 |
| D/Y | rs751001455 |
0.095 | 0.998 | D | 0.798 | 0.463 | 0.728531110816 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/Y | rs751001455 |
0.095 | 0.998 | D | 0.798 | 0.463 | 0.728531110816 | gnomAD-4.0.0 | 1.59249E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85974E-06 | 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 | 0.9033 | likely_pathogenic | 0.9095 | pathogenic | -0.374 | Destabilizing | 0.886 | D | 0.603 | neutral | D | 0.530032308 | None | None | N |
| D/C | 0.9908 | likely_pathogenic | 0.9917 | pathogenic | 0.006 | Stabilizing | 0.986 | D | 0.851 | deleterious | None | None | None | None | N |
| D/E | 0.6476 | likely_pathogenic | 0.6599 | pathogenic | -0.401 | Destabilizing | 0.001 | N | 0.364 | neutral | N | 0.512657268 | None | None | N |
| D/F | 0.9901 | likely_pathogenic | 0.9903 | pathogenic | -0.377 | Destabilizing | 0.999 | D | 0.791 | deleterious | None | None | None | None | N |
| D/G | 0.8945 | likely_pathogenic | 0.9142 | pathogenic | -0.569 | Destabilizing | 0.617 | D | 0.741 | deleterious | N | 0.520896881 | None | None | N |
| D/H | 0.95 | likely_pathogenic | 0.9559 | pathogenic | -0.291 | Destabilizing | 0.988 | D | 0.838 | deleterious | N | 0.509794065 | None | None | N |
| D/I | 0.978 | likely_pathogenic | 0.9769 | pathogenic | 0.093 | Stabilizing | 0.987 | D | 0.8 | deleterious | None | None | None | None | N |
| D/K | 0.9806 | likely_pathogenic | 0.9831 | pathogenic | 0.166 | Stabilizing | 0.949 | D | 0.754 | deleterious | None | None | None | None | N |
| D/L | 0.9694 | likely_pathogenic | 0.9707 | pathogenic | 0.093 | Stabilizing | 0.974 | D | 0.724 | deleterious | None | None | None | None | N |
| D/M | 0.9909 | likely_pathogenic | 0.9912 | pathogenic | 0.305 | Stabilizing | 0.997 | D | 0.846 | deleterious | None | None | None | None | N |
| D/N | 0.5526 | ambiguous | 0.5551 | ambiguous | -0.083 | Destabilizing | 0.777 | D | 0.779 | deleterious | N | 0.478002873 | None | None | N |
| D/P | 0.9742 | likely_pathogenic | 0.977 | pathogenic | -0.041 | Destabilizing | 0.598 | D | 0.789 | deleterious | None | None | None | None | N |
| D/Q | 0.9643 | likely_pathogenic | 0.9688 | pathogenic | -0.063 | Destabilizing | 0.874 | D | 0.821 | deleterious | None | None | None | None | N |
| D/R | 0.9841 | likely_pathogenic | 0.9857 | pathogenic | 0.31 | Stabilizing | 0.974 | D | 0.738 | deleterious | None | None | None | None | N |
| D/S | 0.8077 | likely_pathogenic | 0.8219 | pathogenic | -0.199 | Destabilizing | 0.747 | D | 0.728 | deleterious | None | None | None | None | N |
| D/T | 0.9461 | likely_pathogenic | 0.9478 | pathogenic | -0.052 | Destabilizing | 0.822 | D | 0.787 | deleterious | None | None | None | None | N |
| D/V | 0.9289 | likely_pathogenic | 0.9282 | pathogenic | -0.041 | Destabilizing | 0.909 | D | 0.729 | deleterious | N | 0.514313515 | None | None | N |
| D/W | 0.9978 | likely_pathogenic | 0.998 | pathogenic | -0.26 | Destabilizing | 0.999 | D | 0.807 | deleterious | None | None | None | None | N |
| D/Y | 0.8987 | likely_pathogenic | 0.9068 | pathogenic | -0.154 | Destabilizing | 0.998 | D | 0.798 | deleterious | D | 0.532924749 | 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.