Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18353 | 55282;55283;55284 | chr2:178602345;178602344;178602343 | chr2:179467072;179467071;179467070 |
| N2AB | 16712 | 50359;50360;50361 | chr2:178602345;178602344;178602343 | chr2:179467072;179467071;179467070 |
| N2A | 15785 | 47578;47579;47580 | chr2:178602345;178602344;178602343 | chr2:179467072;179467071;179467070 |
| N2B | 9288 | 28087;28088;28089 | chr2:178602345;178602344;178602343 | chr2:179467072;179467071;179467070 |
| Novex-1 | 9413 | 28462;28463;28464 | chr2:178602345;178602344;178602343 | chr2:179467072;179467071;179467070 |
| Novex-2 | 9480 | 28663;28664;28665 | chr2:178602345;178602344;178602343 | chr2:179467072;179467071;179467070 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | None | None | 1.0 | D | 0.769 | 0.623 | 0.358134431457 | gnomAD-4.0.0 | 1.59317E-06 | None | None | None | None | N | None | 5.67215E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs747601378  |
-0.919 | 0.999 | N | 0.611 | 0.516 | 0.276482976112 | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | N | None | 8.28E-05 | 8.51E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-06 | 1.40805E-04 |
| N/S | rs747601378 |
-0.919 | 0.999 | N | 0.611 | 0.516 | 0.276482976112 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs747601378 |
-0.919 | 0.999 | N | 0.611 | 0.516 | 0.276482976112 | gnomAD-4.0.0 | 8.68034E-06 | None | None | None | None | N | None | 4.00716E-05 | 3.3389E-05 | None | 0 | 2.23644E-05 | None | 0 | 0 | 6.78347E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.976 | likely_pathogenic | 0.985 | pathogenic | -0.189 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| N/C | 0.8543 | likely_pathogenic | 0.9137 | pathogenic | -0.352 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| N/D | 0.9606 | likely_pathogenic | 0.9692 | pathogenic | -2.306 | Highly Destabilizing | 0.999 | D | 0.617 | neutral | D | 0.545796813 | None | None | N |
| N/E | 0.995 | likely_pathogenic | 0.9952 | pathogenic | -2.142 | Highly Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| N/F | 0.9976 | likely_pathogenic | 0.9979 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| N/G | 0.9307 | likely_pathogenic | 0.9535 | pathogenic | -0.481 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| N/H | 0.9308 | likely_pathogenic | 0.9498 | pathogenic | -0.362 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.546303792 | None | None | N |
| N/I | 0.9826 | likely_pathogenic | 0.9847 | pathogenic | 0.537 | Stabilizing | 1.0 | D | 0.803 | deleterious | D | 0.546557282 | None | None | N |
| N/K | 0.9947 | likely_pathogenic | 0.9948 | pathogenic | 0.013 | Stabilizing | 1.0 | D | 0.743 | deleterious | D | 0.545543324 | None | None | N |
| N/L | 0.9458 | likely_pathogenic | 0.9493 | pathogenic | 0.537 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| N/M | 0.9761 | likely_pathogenic | 0.9801 | pathogenic | 0.619 | Stabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| N/P | 0.9928 | likely_pathogenic | 0.9931 | pathogenic | 0.323 | Stabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| N/Q | 0.9935 | likely_pathogenic | 0.9946 | pathogenic | -0.905 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| N/R | 0.9901 | likely_pathogenic | 0.9903 | pathogenic | -0.036 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| N/S | 0.4424 | ambiguous | 0.5782 | pathogenic | -0.757 | Destabilizing | 0.999 | D | 0.611 | neutral | N | 0.497925602 | None | None | N |
| N/T | 0.7752 | likely_pathogenic | 0.8349 | pathogenic | -0.457 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | N | 0.499860931 | None | None | N |
| N/V | 0.9723 | likely_pathogenic | 0.9785 | pathogenic | 0.323 | Stabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| N/W | 0.9986 | likely_pathogenic | 0.999 | pathogenic | -0.387 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| N/Y | 0.9774 | likely_pathogenic | 0.9809 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.813 | deleterious | D | 0.545796813 | 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.