Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31225 | 93898;93899;93900 | chr2:178547953;178547952;178547951 | chr2:179412680;179412679;179412678 |
| N2AB | 29584 | 88975;88976;88977 | chr2:178547953;178547952;178547951 | chr2:179412680;179412679;179412678 |
| N2A | 28657 | 86194;86195;86196 | chr2:178547953;178547952;178547951 | chr2:179412680;179412679;179412678 |
| N2B | 22160 | 66703;66704;66705 | chr2:178547953;178547952;178547951 | chr2:179412680;179412679;179412678 |
| Novex-1 | 22285 | 67078;67079;67080 | chr2:178547953;178547952;178547951 | chr2:179412680;179412679;179412678 |
| Novex-2 | 22352 | 67279;67280;67281 | chr2:178547953;178547952;178547951 | chr2:179412680;179412679;179412678 |
| 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 | rs727505175  |
-1.808 | 0.939 | N | 0.616 | 0.621 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 0 |
| I/T | rs727505175 |
-1.808 | 0.939 | N | 0.616 | 0.621 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| I/T | rs727505175 |
-1.808 | 0.939 | N | 0.616 | 0.621 | None | gnomAD-4.0.0 | 5.32957E-05 | None | None | None | None | I | None | 1.3349E-05 | 1.66778E-05 | None | 0 | 0 | None | 0 | 0 | 6.86571E-05 | 0 | 4.80307E-05 |
| I/V | rs529500497 |
-0.867 | 0.02 | N | 0.236 | 0.082 | 0.554558929491 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.67616E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs529500497 |
-0.867 | 0.02 | N | 0.236 | 0.082 | 0.554558929491 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 5.7759E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs529500497 |
-0.867 | 0.02 | N | 0.236 | 0.082 | 0.554558929491 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/V | rs529500497 |
-0.867 | 0.02 | N | 0.236 | 0.082 | 0.554558929491 | gnomAD-4.0.0 | 4.95732E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.56104E-04 | None | 0 | 0 | 8.47624E-07 | 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 | 0.8694 | likely_pathogenic | 0.8697 | pathogenic | -2.067 | Highly Destabilizing | 0.91 | D | 0.557 | neutral | None | None | None | None | I |
| I/C | 0.8923 | likely_pathogenic | 0.8829 | pathogenic | -1.414 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | I |
| I/D | 0.9842 | likely_pathogenic | 0.9851 | pathogenic | -1.895 | Destabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | I |
| I/E | 0.9406 | likely_pathogenic | 0.9403 | pathogenic | -1.687 | Destabilizing | 0.993 | D | 0.788 | deleterious | None | None | None | None | I |
| I/F | 0.295 | likely_benign | 0.2859 | benign | -1.135 | Destabilizing | 0.986 | D | 0.623 | neutral | None | None | None | None | I |
| I/G | 0.974 | likely_pathogenic | 0.9733 | pathogenic | -2.598 | Highly Destabilizing | 0.993 | D | 0.775 | deleterious | None | None | None | None | I |
| I/H | 0.8523 | likely_pathogenic | 0.836 | pathogenic | -2.0 | Highly Destabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | I |
| I/K | 0.8316 | likely_pathogenic | 0.808 | pathogenic | -1.556 | Destabilizing | 0.991 | D | 0.788 | deleterious | N | 0.502306235 | None | None | I |
| I/L | 0.149 | likely_benign | 0.1518 | benign | -0.564 | Destabilizing | 0.58 | D | 0.433 | neutral | N | 0.485726957 | None | None | I |
| I/M | 0.2095 | likely_benign | 0.2024 | benign | -0.541 | Destabilizing | 0.991 | D | 0.633 | neutral | N | 0.493405465 | None | None | I |
| I/N | 0.8795 | likely_pathogenic | 0.876 | pathogenic | -1.826 | Destabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | I |
| I/P | 0.9843 | likely_pathogenic | 0.9842 | pathogenic | -1.042 | Destabilizing | 0.998 | D | 0.789 | deleterious | None | None | None | None | I |
| I/Q | 0.8352 | likely_pathogenic | 0.8253 | pathogenic | -1.674 | Destabilizing | 0.998 | D | 0.786 | deleterious | None | None | None | None | I |
| I/R | 0.783 | likely_pathogenic | 0.7564 | pathogenic | -1.353 | Destabilizing | 0.991 | D | 0.787 | deleterious | N | 0.520917469 | None | None | I |
| I/S | 0.8838 | likely_pathogenic | 0.8767 | pathogenic | -2.564 | Highly Destabilizing | 0.993 | D | 0.687 | prob.neutral | None | None | None | None | I |
| I/T | 0.8134 | likely_pathogenic | 0.7997 | pathogenic | -2.198 | Highly Destabilizing | 0.939 | D | 0.616 | neutral | N | 0.496772827 | None | None | I |
| I/V | 0.1179 | likely_benign | 0.1169 | benign | -1.042 | Destabilizing | 0.02 | N | 0.236 | neutral | N | 0.470216 | None | None | I |
| I/W | 0.8974 | likely_pathogenic | 0.8885 | pathogenic | -1.46 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| I/Y | 0.7294 | likely_pathogenic | 0.7044 | pathogenic | -1.133 | Destabilizing | 0.993 | D | 0.689 | prob.neutral | None | None | None | None | I |
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.