Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15506 | 46741;46742;46743 | chr2:178619801;178619800;178619799 | chr2:179484528;179484527;179484526 |
| N2AB | 13865 | 41818;41819;41820 | chr2:178619801;178619800;178619799 | chr2:179484528;179484527;179484526 |
| N2A | 12938 | 39037;39038;39039 | chr2:178619801;178619800;178619799 | chr2:179484528;179484527;179484526 |
| N2B | 6441 | 19546;19547;19548 | chr2:178619801;178619800;178619799 | chr2:179484528;179484527;179484526 |
| Novex-1 | 6566 | 19921;19922;19923 | chr2:178619801;178619800;178619799 | chr2:179484528;179484527;179484526 |
| Novex-2 | 6633 | 20122;20123;20124 | chr2:178619801;178619800;178619799 | chr2:179484528;179484527;179484526 |
| 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/H | rs755611206  |
-0.034 | 0.997 | D | 0.715 | 0.653 | 0.509937682487 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 1.40607E-04 |
| D/H | rs755611206 |
-0.034 | 0.997 | D | 0.715 | 0.653 | 0.509937682487 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 6.58E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| D/H | rs755611206 |
-0.034 | 0.997 | D | 0.715 | 0.653 | 0.509937682487 | gnomAD-4.0.0 | 3.28747E-05 | None | None | None | None | N | None | 0 | 1.67062E-05 | None | 0 | 0 | None | 0 | 0 | 4.24121E-05 | 0 | 3.20616E-05 |
| D/V | rs748069813 |
0.237 | 0.978 | D | 0.721 | 0.736 | 0.820832588438 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/V | rs748069813 |
0.237 | 0.978 | D | 0.721 | 0.736 | 0.820832588438 | gnomAD-4.0.0 | 1.59429E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43398E-05 | 0 |
| D/Y | rs755611206 |
None | 0.997 | D | 0.737 | 0.64 | 0.782613236998 | gnomAD-4.0.0 | 6.84772E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65854E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5255 | ambiguous | 0.7481 | pathogenic | -0.197 | Destabilizing | 0.957 | D | 0.683 | prob.neutral | D | 0.536372632 | None | None | N |
| D/C | 0.9354 | likely_pathogenic | 0.9786 | pathogenic | -0.067 | Destabilizing | 0.999 | D | 0.74 | deleterious | None | None | None | None | N |
| D/E | 0.2976 | likely_benign | 0.47 | ambiguous | -0.283 | Destabilizing | 0.726 | D | 0.499 | neutral | N | 0.517773665 | None | None | N |
| D/F | 0.9258 | likely_pathogenic | 0.973 | pathogenic | -0.095 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/G | 0.4604 | ambiguous | 0.6693 | pathogenic | -0.392 | Destabilizing | 0.928 | D | 0.701 | prob.neutral | N | 0.51358628 | None | None | N |
| D/H | 0.7545 | likely_pathogenic | 0.8789 | pathogenic | 0.171 | Stabilizing | 0.997 | D | 0.715 | prob.delet. | D | 0.547129482 | None | None | N |
| D/I | 0.8541 | likely_pathogenic | 0.947 | pathogenic | 0.265 | Stabilizing | 0.992 | D | 0.75 | deleterious | None | None | None | None | N |
| D/K | 0.8102 | likely_pathogenic | 0.9109 | pathogenic | 0.28 | Stabilizing | 0.968 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/L | 0.8138 | likely_pathogenic | 0.921 | pathogenic | 0.265 | Stabilizing | 0.983 | D | 0.72 | prob.delet. | None | None | None | None | N |
| D/M | 0.9225 | likely_pathogenic | 0.9747 | pathogenic | 0.26 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | N |
| D/N | 0.2904 | likely_benign | 0.4442 | ambiguous | -0.022 | Destabilizing | 0.978 | D | 0.733 | prob.delet. | D | 0.544566603 | None | None | N |
| D/P | 0.7572 | likely_pathogenic | 0.8717 | pathogenic | 0.133 | Stabilizing | 0.992 | D | 0.733 | prob.delet. | None | None | None | None | N |
| D/Q | 0.7475 | likely_pathogenic | 0.8752 | pathogenic | 0.015 | Stabilizing | 0.345 | N | 0.511 | neutral | None | None | None | None | N |
| D/R | 0.8408 | likely_pathogenic | 0.9199 | pathogenic | 0.513 | Stabilizing | 0.968 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/S | 0.4028 | ambiguous | 0.6143 | pathogenic | -0.134 | Destabilizing | 0.895 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/T | 0.6759 | likely_pathogenic | 0.8544 | pathogenic | 0.017 | Stabilizing | 0.983 | D | 0.708 | prob.delet. | None | None | None | None | N |
| D/V | 0.6638 | likely_pathogenic | 0.8521 | pathogenic | 0.133 | Stabilizing | 0.978 | D | 0.721 | prob.delet. | D | 0.547790484 | None | None | N |
| D/W | 0.972 | likely_pathogenic | 0.9879 | pathogenic | 0.029 | Stabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | N |
| D/Y | 0.6256 | likely_pathogenic | 0.7835 | pathogenic | 0.142 | Stabilizing | 0.997 | D | 0.737 | prob.delet. | D | 0.546967325 | 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.