Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15729 | 47410;47411;47412 | chr2:178618273;178618272;178618271 | chr2:179483000;179482999;179482998 |
| N2AB | 14088 | 42487;42488;42489 | chr2:178618273;178618272;178618271 | chr2:179483000;179482999;179482998 |
| N2A | 13161 | 39706;39707;39708 | chr2:178618273;178618272;178618271 | chr2:179483000;179482999;179482998 |
| N2B | 6664 | 20215;20216;20217 | chr2:178618273;178618272;178618271 | chr2:179483000;179482999;179482998 |
| Novex-1 | 6789 | 20590;20591;20592 | chr2:178618273;178618272;178618271 | chr2:179483000;179482999;179482998 |
| Novex-2 | 6856 | 20791;20792;20793 | chr2:178618273;178618272;178618271 | chr2:179483000;179482999;179482998 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | None | None | 0.999 | N | 0.543 | 0.21 | 0.343334270461 | 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 |
| L/P | rs1364835059  |
None | 1.0 | D | 0.747 | 0.651 | 0.767801976584 | 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 |
| L/P | rs1364835059 |
None | 1.0 | D | 0.747 | 0.651 | 0.767801976584 | gnomAD-4.0.0 | 6.58137E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47262E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.5044 | ambiguous | 0.4635 | ambiguous | -2.516 | Highly Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| L/C | 0.5743 | likely_pathogenic | 0.4696 | ambiguous | -1.503 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| L/D | 0.9475 | likely_pathogenic | 0.9225 | pathogenic | -2.977 | Highly Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| L/E | 0.6724 | likely_pathogenic | 0.6205 | pathogenic | -2.722 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| L/F | 0.1755 | likely_benign | 0.1676 | benign | -1.408 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| L/G | 0.8578 | likely_pathogenic | 0.8227 | pathogenic | -3.04 | Highly Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| L/H | 0.3547 | ambiguous | 0.294 | benign | -2.623 | Highly Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/I | 0.1171 | likely_benign | 0.1133 | benign | -0.971 | Destabilizing | 0.999 | D | 0.543 | neutral | N | 0.478200631 | None | None | N |
| L/K | 0.4261 | ambiguous | 0.3413 | ambiguous | -1.747 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| L/M | 0.158 | likely_benign | 0.1615 | benign | -1.005 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| L/N | 0.7366 | likely_pathogenic | 0.6649 | pathogenic | -2.18 | Highly Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| L/P | 0.9878 | likely_pathogenic | 0.982 | pathogenic | -1.473 | Destabilizing | 1.0 | D | 0.747 | deleterious | D | 0.590753991 | None | None | N |
| L/Q | 0.2476 | likely_benign | 0.2237 | benign | -1.967 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.462434512 | None | None | N |
| L/R | 0.2805 | likely_benign | 0.2348 | benign | -1.617 | Destabilizing | 1.0 | D | 0.67 | neutral | N | 0.457674488 | None | None | N |
| L/S | 0.5824 | likely_pathogenic | 0.5486 | ambiguous | -2.755 | Highly Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | N |
| L/T | 0.4509 | ambiguous | 0.3912 | ambiguous | -2.371 | Highly Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| L/V | 0.122 | likely_benign | 0.1186 | benign | -1.473 | Destabilizing | 0.999 | D | 0.571 | neutral | N | 0.472551928 | None | None | N |
| L/W | 0.4025 | ambiguous | 0.3839 | ambiguous | -1.854 | Destabilizing | 1.0 | D | 0.646 | neutral | None | None | None | None | N |
| L/Y | 0.4013 | ambiguous | 0.3549 | ambiguous | -1.588 | Destabilizing | 1.0 | D | 0.675 | prob.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.