Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19381 | 58366;58367;58368 | chr2:178594353;178594352;178594351 | chr2:179459080;179459079;179459078 |
| N2AB | 17740 | 53443;53444;53445 | chr2:178594353;178594352;178594351 | chr2:179459080;179459079;179459078 |
| N2A | 16813 | 50662;50663;50664 | chr2:178594353;178594352;178594351 | chr2:179459080;179459079;179459078 |
| N2B | 10316 | 31171;31172;31173 | chr2:178594353;178594352;178594351 | chr2:179459080;179459079;179459078 |
| Novex-1 | 10441 | 31546;31547;31548 | chr2:178594353;178594352;178594351 | chr2:179459080;179459079;179459078 |
| Novex-2 | 10508 | 31747;31748;31749 | chr2:178594353;178594352;178594351 | chr2:179459080;179459079;179459078 |
| 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 | None | None | 0.982 | N | 0.546 | 0.146 | 0.330331372229 | gnomAD-4.0.0 | 1.20035E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66354E-05 |
| D/N | rs1325584288  |
0.457 | 0.998 | N | 0.733 | 0.332 | 0.330331372229 | gnomAD-2.1.1 | 4.3E-06 | None | None | None | None | N | None | 0 | 3.2E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1325584288 |
0.457 | 0.998 | N | 0.733 | 0.332 | 0.330331372229 | gnomAD-4.0.0 | 1.64633E-06 | None | None | None | None | N | None | 0 | 2.48398E-05 | None | 0 | 0 | None | 0 | 0 | 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 | 0.6809 | likely_pathogenic | 0.6061 | pathogenic | -0.174 | Destabilizing | 0.982 | D | 0.566 | neutral | N | 0.498215386 | None | None | N |
| D/C | 0.9693 | likely_pathogenic | 0.9603 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| D/E | 0.414 | ambiguous | 0.3684 | ambiguous | -0.263 | Destabilizing | 0.982 | D | 0.546 | neutral | N | 0.482536644 | None | None | N |
| D/F | 0.9819 | likely_pathogenic | 0.9717 | pathogenic | -0.22 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/G | 0.7047 | likely_pathogenic | 0.6521 | pathogenic | -0.343 | Destabilizing | 0.991 | D | 0.686 | prob.delet. | N | 0.489758847 | None | None | N |
| D/H | 0.8973 | likely_pathogenic | 0.8688 | pathogenic | 0.003 | Stabilizing | 1.0 | D | 0.799 | deleterious | N | 0.480937437 | None | None | N |
| D/I | 0.9453 | likely_pathogenic | 0.9153 | pathogenic | 0.213 | Stabilizing | 0.999 | D | 0.739 | deleterious | None | None | None | None | N |
| D/K | 0.9339 | likely_pathogenic | 0.9087 | pathogenic | 0.329 | Stabilizing | 0.698 | D | 0.403 | neutral | None | None | None | None | N |
| D/L | 0.9044 | likely_pathogenic | 0.8751 | pathogenic | 0.213 | Stabilizing | 0.998 | D | 0.684 | prob.delet. | None | None | None | None | N |
| D/M | 0.9617 | likely_pathogenic | 0.9436 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| D/N | 0.3046 | likely_benign | 0.2764 | benign | 0.138 | Stabilizing | 0.998 | D | 0.733 | deleterious | N | 0.473429019 | None | None | N |
| D/P | 0.9361 | likely_pathogenic | 0.9207 | pathogenic | 0.106 | Stabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| D/Q | 0.902 | likely_pathogenic | 0.8685 | pathogenic | 0.148 | Stabilizing | 0.996 | D | 0.749 | deleterious | None | None | None | None | N |
| D/R | 0.9566 | likely_pathogenic | 0.9389 | pathogenic | 0.483 | Stabilizing | 0.992 | D | 0.7 | prob.delet. | None | None | None | None | N |
| D/S | 0.5701 | likely_pathogenic | 0.5129 | ambiguous | 0.019 | Stabilizing | 0.987 | D | 0.698 | prob.delet. | None | None | None | None | N |
| D/T | 0.8245 | likely_pathogenic | 0.7749 | pathogenic | 0.145 | Stabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| D/V | 0.8419 | likely_pathogenic | 0.7788 | pathogenic | 0.106 | Stabilizing | 0.998 | D | 0.681 | prob.neutral | N | 0.484949908 | None | None | N |
| D/W | 0.9944 | likely_pathogenic | 0.992 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| D/Y | 0.8521 | likely_pathogenic | 0.7976 | pathogenic | 0.004 | Stabilizing | 1.0 | D | 0.761 | deleterious | N | 0.503561142 | 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.