Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15048 | 45367;45368;45369 | chr2:178621682;178621681;178621680 | chr2:179486409;179486408;179486407 |
| N2AB | 13407 | 40444;40445;40446 | chr2:178621682;178621681;178621680 | chr2:179486409;179486408;179486407 |
| N2A | 12480 | 37663;37664;37665 | chr2:178621682;178621681;178621680 | chr2:179486409;179486408;179486407 |
| N2B | 5983 | 18172;18173;18174 | chr2:178621682;178621681;178621680 | chr2:179486409;179486408;179486407 |
| Novex-1 | 6108 | 18547;18548;18549 | chr2:178621682;178621681;178621680 | chr2:179486409;179486408;179486407 |
| Novex-2 | 6175 | 18748;18749;18750 | chr2:178621682;178621681;178621680 | chr2:179486409;179486408;179486407 |
| 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/K | rs727505261  |
-2.306 | 0.484 | D | 0.733 | 0.634 | 0.831925844807 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.02E-06 | 0 |
| I/K | rs727505261 |
-2.306 | 0.484 | D | 0.733 | 0.634 | 0.831925844807 | gnomAD-4.0.0 | 6.84814E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99954E-07 | 0 | 0 |
| I/T | rs727505261 |
-2.996 | 0.062 | D | 0.641 | 0.486 | 0.67026131262 | gnomAD-2.1.1 | 8.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| I/T | rs727505261 |
-2.996 | 0.062 | D | 0.641 | 0.486 | 0.67026131262 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| I/T | rs727505261 |
-2.996 | 0.062 | D | 0.641 | 0.486 | 0.67026131262 | gnomAD-4.0.0 | 1.17857E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.24155E-05 | None | 0 | 0 | 1.35702E-05 | 0 | 3.20718E-05 |
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 | 0.5817 | likely_pathogenic | 0.6195 | pathogenic | -2.738 | Highly Destabilizing | 0.035 | N | 0.513 | neutral | None | None | None | None | N |
| I/C | 0.8689 | likely_pathogenic | 0.8568 | pathogenic | -1.995 | Destabilizing | 0.824 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/D | 0.9877 | likely_pathogenic | 0.9819 | pathogenic | -3.189 | Highly Destabilizing | 0.555 | D | 0.741 | deleterious | None | None | None | None | N |
| I/E | 0.9631 | likely_pathogenic | 0.9501 | pathogenic | -2.942 | Highly Destabilizing | 0.555 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/F | 0.543 | ambiguous | 0.3629 | ambiguous | -1.655 | Destabilizing | 0.38 | N | 0.687 | prob.neutral | None | None | None | None | N |
| I/G | 0.9263 | likely_pathogenic | 0.9259 | pathogenic | -3.305 | Highly Destabilizing | 0.262 | N | 0.692 | prob.neutral | None | None | None | None | N |
| I/H | 0.9682 | likely_pathogenic | 0.9356 | pathogenic | -2.684 | Highly Destabilizing | 0.935 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/K | 0.9348 | likely_pathogenic | 0.9012 | pathogenic | -2.344 | Highly Destabilizing | 0.484 | N | 0.733 | prob.delet. | D | 0.613243182 | None | None | N |
| I/L | 0.2175 | likely_benign | 0.1736 | benign | -1.085 | Destabilizing | 0.005 | N | 0.419 | neutral | D | 0.528468547 | None | None | N |
| I/M | 0.1865 | likely_benign | 0.1667 | benign | -0.949 | Destabilizing | 0.317 | N | 0.655 | neutral | D | 0.599966027 | None | None | N |
| I/N | 0.8811 | likely_pathogenic | 0.8443 | pathogenic | -2.753 | Highly Destabilizing | 0.791 | D | 0.747 | deleterious | None | None | None | None | N |
| I/P | 0.9835 | likely_pathogenic | 0.9732 | pathogenic | -1.619 | Destabilizing | 0.791 | D | 0.743 | deleterious | None | None | None | None | N |
| I/Q | 0.9285 | likely_pathogenic | 0.9 | pathogenic | -2.594 | Highly Destabilizing | 0.791 | D | 0.746 | deleterious | None | None | None | None | N |
| I/R | 0.901 | likely_pathogenic | 0.848 | pathogenic | -2.016 | Highly Destabilizing | 0.484 | N | 0.747 | deleterious | D | 0.691734212 | None | None | N |
| I/S | 0.7804 | likely_pathogenic | 0.7725 | pathogenic | -3.434 | Highly Destabilizing | 0.149 | N | 0.677 | prob.neutral | None | None | None | None | N |
| I/T | 0.7085 | likely_pathogenic | 0.6296 | pathogenic | -3.033 | Highly Destabilizing | 0.062 | N | 0.641 | neutral | D | 0.544049036 | None | None | N |
| I/V | 0.0892 | likely_benign | 0.0689 | benign | -1.619 | Destabilizing | None | N | 0.173 | neutral | N | 0.386666366 | None | None | N |
| I/W | 0.9795 | likely_pathogenic | 0.9493 | pathogenic | -2.053 | Highly Destabilizing | 0.935 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/Y | 0.9109 | likely_pathogenic | 0.8357 | pathogenic | -1.774 | Destabilizing | 0.555 | D | 0.737 | prob.delet. | 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.