Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33298 | 100117;100118;100119 | chr2:178537217;178537216;178537215 | chr2:179401944;179401943;179401942 |
| N2AB | 31657 | 95194;95195;95196 | chr2:178537217;178537216;178537215 | chr2:179401944;179401943;179401942 |
| N2A | 30730 | 92413;92414;92415 | chr2:178537217;178537216;178537215 | chr2:179401944;179401943;179401942 |
| N2B | 24233 | 72922;72923;72924 | chr2:178537217;178537216;178537215 | chr2:179401944;179401943;179401942 |
| Novex-1 | 24358 | 73297;73298;73299 | chr2:178537217;178537216;178537215 | chr2:179401944;179401943;179401942 |
| Novex-2 | 24425 | 73498;73499;73500 | chr2:178537217;178537216;178537215 | chr2:179401944;179401943;179401942 |
| 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/M | rs1487906230  |
None | 0.331 | N | 0.677 | 0.059 | 0.29385284311 | gnomAD-4.0.0 | 3.2094E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.78336E-06 | 0 | 0 |
| I/T | rs768876552 |
-2.609 | 0.22 | N | 0.701 | 0.321 | 0.570896731233 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 4.14E-05 | 2.84E-05 | None | 0 | 1.02617E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs768876552 |
-2.609 | 0.22 | N | 0.701 | 0.321 | 0.570896731233 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.15429E-03 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs768876552 |
-2.609 | 0.22 | N | 0.701 | 0.321 | 0.570896731233 | gnomAD-4.0.0 | 6.83855E-06 | None | None | None | None | N | None | 1.33536E-05 | 1.67112E-05 | None | 0 | 2.00992E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1056550326 |
None | 0.004 | N | 0.203 | 0.055 | 0.29527378943 | gnomAD-4.0.0 | 1.37353E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80568E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7532 | likely_pathogenic | 0.7428 | pathogenic | -2.048 | Highly Destabilizing | 0.272 | N | 0.643 | neutral | None | None | None | None | N |
| I/C | 0.9471 | likely_pathogenic | 0.9574 | pathogenic | -1.447 | Destabilizing | 0.968 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/D | 0.9969 | likely_pathogenic | 0.9974 | pathogenic | -1.987 | Destabilizing | 0.89 | D | 0.791 | deleterious | None | None | None | None | N |
| I/E | 0.9916 | likely_pathogenic | 0.9925 | pathogenic | -1.774 | Destabilizing | 0.726 | D | 0.775 | deleterious | None | None | None | None | N |
| I/F | 0.6197 | likely_pathogenic | 0.6908 | pathogenic | -1.034 | Destabilizing | 0.331 | N | 0.669 | neutral | N | 0.513766415 | None | None | N |
| I/G | 0.9832 | likely_pathogenic | 0.9853 | pathogenic | -2.579 | Highly Destabilizing | 0.726 | D | 0.765 | deleterious | None | None | None | None | N |
| I/H | 0.9932 | likely_pathogenic | 0.9953 | pathogenic | -2.079 | Highly Destabilizing | 0.968 | D | 0.783 | deleterious | None | None | None | None | N |
| I/K | 0.9873 | likely_pathogenic | 0.9898 | pathogenic | -1.591 | Destabilizing | 0.726 | D | 0.775 | deleterious | None | None | None | None | N |
| I/L | 0.1492 | likely_benign | 0.1581 | benign | -0.54 | Destabilizing | None | N | 0.235 | neutral | N | 0.458105134 | None | None | N |
| I/M | 0.2206 | likely_benign | 0.2536 | benign | -0.621 | Destabilizing | 0.331 | N | 0.677 | prob.neutral | N | 0.487273247 | None | None | N |
| I/N | 0.9709 | likely_pathogenic | 0.9779 | pathogenic | -1.842 | Destabilizing | 0.859 | D | 0.795 | deleterious | N | 0.493459058 | None | None | N |
| I/P | 0.9333 | likely_pathogenic | 0.9482 | pathogenic | -1.02 | Destabilizing | 0.89 | D | 0.787 | deleterious | None | None | None | None | N |
| I/Q | 0.9859 | likely_pathogenic | 0.9889 | pathogenic | -1.682 | Destabilizing | 0.89 | D | 0.789 | deleterious | None | None | None | None | N |
| I/R | 0.9799 | likely_pathogenic | 0.9845 | pathogenic | -1.424 | Destabilizing | 0.726 | D | 0.791 | deleterious | None | None | None | None | N |
| I/S | 0.9404 | likely_pathogenic | 0.9492 | pathogenic | -2.554 | Highly Destabilizing | 0.667 | D | 0.71 | prob.delet. | N | 0.483073349 | None | None | N |
| I/T | 0.7839 | likely_pathogenic | 0.802 | pathogenic | -2.194 | Highly Destabilizing | 0.22 | N | 0.701 | prob.neutral | N | 0.506336224 | None | None | N |
| I/V | 0.079 | likely_benign | 0.0786 | benign | -1.02 | Destabilizing | 0.004 | N | 0.203 | neutral | N | 0.423299127 | None | None | N |
| I/W | 0.9905 | likely_pathogenic | 0.9938 | pathogenic | -1.391 | Destabilizing | 0.968 | D | 0.767 | deleterious | None | None | None | None | N |
| I/Y | 0.9685 | likely_pathogenic | 0.977 | pathogenic | -1.065 | Destabilizing | 0.726 | D | 0.704 | 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.