Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17851 | 53776;53777;53778 | chr2:178607051;178607050;178607049 | chr2:179471778;179471777;179471776 |
| N2AB | 16210 | 48853;48854;48855 | chr2:178607051;178607050;178607049 | chr2:179471778;179471777;179471776 |
| N2A | 15283 | 46072;46073;46074 | chr2:178607051;178607050;178607049 | chr2:179471778;179471777;179471776 |
| N2B | 8786 | 26581;26582;26583 | chr2:178607051;178607050;178607049 | chr2:179471778;179471777;179471776 |
| Novex-1 | 8911 | 26956;26957;26958 | chr2:178607051;178607050;178607049 | chr2:179471778;179471777;179471776 |
| Novex-2 | 8978 | 27157;27158;27159 | chr2:178607051;178607050;178607049 | chr2:179471778;179471777;179471776 |
| 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/T | rs1458259896  |
None | 0.001 | N | 0.373 | 0.208 | 0.296329037015 | gnomAD-4.0.0 | 2.74079E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73853E-04 | 2.70037E-06 | 0 | 0 |
| I/V | rs1472380264 |
-1.036 | 0.001 | N | 0.265 | 0.082 | 0.218845423259 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.32E-05 | None | 0 | 0 | 0 |
| I/V | rs1472380264 |
-1.036 | 0.001 | N | 0.265 | 0.082 | 0.218845423259 | gnomAD-4.0.0 | 1.59628E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44417E-05 | 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 | 0.2921 | likely_benign | 0.3422 | ambiguous | -2.048 | Highly Destabilizing | 0.057 | N | 0.495 | neutral | None | None | None | None | N |
| I/C | 0.7179 | likely_pathogenic | 0.7789 | pathogenic | -1.297 | Destabilizing | 0.887 | D | 0.571 | neutral | None | None | None | None | N |
| I/D | 0.8992 | likely_pathogenic | 0.9165 | pathogenic | -2.287 | Highly Destabilizing | 0.507 | D | 0.706 | prob.delet. | None | None | None | None | N |
| I/E | 0.7821 | likely_pathogenic | 0.8251 | pathogenic | -2.124 | Highly Destabilizing | 0.507 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/F | 0.2874 | likely_benign | 0.3674 | ambiguous | -1.195 | Destabilizing | 0.507 | D | 0.551 | neutral | None | None | None | None | N |
| I/G | 0.8288 | likely_pathogenic | 0.8368 | pathogenic | -2.518 | Highly Destabilizing | 0.227 | N | 0.691 | prob.delet. | None | None | None | None | N |
| I/H | 0.8053 | likely_pathogenic | 0.8581 | pathogenic | -1.892 | Destabilizing | 0.96 | D | 0.743 | deleterious | None | None | None | None | N |
| I/K | 0.7306 | likely_pathogenic | 0.7891 | pathogenic | -1.723 | Destabilizing | 0.437 | N | 0.692 | prob.delet. | N | 0.4731678 | None | None | N |
| I/L | 0.0935 | likely_benign | 0.1101 | benign | -0.734 | Destabilizing | None | N | 0.2 | neutral | N | 0.369501927 | None | None | N |
| I/M | 0.0889 | likely_benign | 0.101 | benign | -0.597 | Destabilizing | 0.437 | N | 0.543 | neutral | N | 0.473341158 | None | None | N |
| I/N | 0.5793 | likely_pathogenic | 0.5937 | pathogenic | -1.917 | Destabilizing | 0.507 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/P | 0.9529 | likely_pathogenic | 0.95 | pathogenic | -1.148 | Destabilizing | 0.676 | D | 0.711 | prob.delet. | None | None | None | None | N |
| I/Q | 0.7164 | likely_pathogenic | 0.7781 | pathogenic | -1.877 | Destabilizing | 0.676 | D | 0.721 | deleterious | None | None | None | None | N |
| I/R | 0.6707 | likely_pathogenic | 0.735 | pathogenic | -1.324 | Destabilizing | 0.437 | N | 0.715 | prob.delet. | N | 0.491580202 | None | None | N |
| I/S | 0.4414 | ambiguous | 0.4499 | ambiguous | -2.518 | Highly Destabilizing | 0.128 | N | 0.57 | neutral | None | None | None | None | N |
| I/T | 0.1144 | likely_benign | 0.1223 | benign | -2.222 | Highly Destabilizing | 0.001 | N | 0.373 | neutral | N | 0.369328569 | None | None | N |
| I/V | 0.0931 | likely_benign | 0.1088 | benign | -1.148 | Destabilizing | 0.001 | N | 0.265 | neutral | N | 0.4282408 | None | None | N |
| I/W | 0.8634 | likely_pathogenic | 0.897 | pathogenic | -1.539 | Destabilizing | 0.96 | D | 0.764 | deleterious | None | None | None | None | N |
| I/Y | 0.7413 | likely_pathogenic | 0.793 | pathogenic | -1.216 | Destabilizing | 0.676 | D | 0.603 | 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.