Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5683 | 17272;17273;17274 | chr2:178731828;178731827;178731826 | chr2:179596555;179596554;179596553 |
| N2AB | 5366 | 16321;16322;16323 | chr2:178731828;178731827;178731826 | chr2:179596555;179596554;179596553 |
| N2A | 4439 | 13540;13541;13542 | chr2:178731828;178731827;178731826 | chr2:179596555;179596554;179596553 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs72648942  |
-1.57 | 0.035 | N | 0.449 | 0.421 | None | gnomAD-2.1.1 | 5.44899E-03 | None | None | None | None | N | None | 1.36431E-03 | 1.75339E-03 | None | 1.02574E-02 | 1.0247E-04 | None | 5.58824E-03 | None | 3.67647E-03 | 7.97448E-03 | 5.61798E-03 |
| Y/C | rs72648942 |
-1.57 | 0.035 | N | 0.449 | 0.421 | None | gnomAD-3.1.2 | 4.69132E-03 | None | None | None | None | N | None | 1.30265E-03 | 3.27397E-03 | 0 | 8.06916E-03 | 1.9253E-04 | None | 4.98871E-03 | 3.16456E-03 | 7.46707E-03 | 3.51676E-03 | 9.57854E-04 |
| Y/C | rs72648942 |
-1.57 | 0.035 | N | 0.449 | 0.421 | None | 1000 genomes | 1.99681E-03 | None | None | None | None | N | None | 8E-04 | 7.2E-03 | None | None | 0 | 2E-03 | None | None | None | 2E-03 | None |
| Y/C | rs72648942 |
-1.57 | 0.035 | N | 0.449 | 0.421 | None | gnomAD-4.0.0 | 6.7162E-03 | None | None | None | None | N | None | 1.29254E-03 | 2.39952E-03 | None | 9.42631E-03 | 6.68539E-05 | None | 4.13894E-03 | 2.80436E-03 | 7.72101E-03 | 6.23573E-03 | 5.71456E-03 |
| Y/D | rs371062603 |
-3.134 | 0.884 | D | 0.643 | 0.56 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/D | rs371062603 |
-3.134 | 0.884 | D | 0.643 | 0.56 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/D | rs371062603 |
-3.134 | 0.884 | D | 0.643 | 0.56 | None | gnomAD-4.0.0 | 1.31451E-05 | None | None | None | None | N | None | 4.82765E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8149 | likely_pathogenic | 0.8043 | pathogenic | -2.606 | Highly Destabilizing | 0.59 | D | 0.557 | neutral | None | None | None | None | N |
| Y/C | 0.231 | likely_benign | 0.217 | benign | -1.773 | Destabilizing | 0.035 | N | 0.449 | neutral | N | 0.509169544 | None | None | N |
| Y/D | 0.8445 | likely_pathogenic | 0.8121 | pathogenic | -2.392 | Highly Destabilizing | 0.884 | D | 0.643 | neutral | D | 0.524818263 | None | None | N |
| Y/E | 0.8972 | likely_pathogenic | 0.878 | pathogenic | -2.205 | Highly Destabilizing | 0.91 | D | 0.575 | neutral | None | None | None | None | N |
| Y/F | 0.1339 | likely_benign | 0.122 | benign | -0.878 | Destabilizing | 0.815 | D | 0.537 | neutral | N | 0.501485843 | None | None | N |
| Y/G | 0.7799 | likely_pathogenic | 0.7638 | pathogenic | -3.025 | Highly Destabilizing | 0.742 | D | 0.603 | neutral | None | None | None | None | N |
| Y/H | 0.3423 | ambiguous | 0.2776 | benign | -1.591 | Destabilizing | 0.003 | N | 0.151 | neutral | N | 0.50781717 | None | None | N |
| Y/I | 0.602 | likely_pathogenic | 0.6058 | pathogenic | -1.255 | Destabilizing | 0.91 | D | 0.575 | neutral | None | None | None | None | N |
| Y/K | 0.8902 | likely_pathogenic | 0.8698 | pathogenic | -1.958 | Destabilizing | 0.91 | D | 0.58 | neutral | None | None | None | None | N |
| Y/L | 0.6564 | likely_pathogenic | 0.657 | pathogenic | -1.255 | Destabilizing | 0.59 | D | 0.521 | neutral | None | None | None | None | N |
| Y/M | 0.7384 | likely_pathogenic | 0.7398 | pathogenic | -1.128 | Destabilizing | 0.996 | D | 0.578 | neutral | None | None | None | None | N |
| Y/N | 0.4215 | ambiguous | 0.3915 | ambiguous | -2.666 | Highly Destabilizing | 0.884 | D | 0.58 | neutral | N | 0.506460519 | None | None | N |
| Y/P | 0.9798 | likely_pathogenic | 0.9762 | pathogenic | -1.713 | Destabilizing | 0.984 | D | 0.7 | prob.neutral | None | None | None | None | N |
| Y/Q | 0.7588 | likely_pathogenic | 0.7251 | pathogenic | -2.398 | Highly Destabilizing | 0.91 | D | 0.613 | neutral | None | None | None | None | N |
| Y/R | 0.7906 | likely_pathogenic | 0.7532 | pathogenic | -1.766 | Destabilizing | 0.91 | D | 0.615 | neutral | None | None | None | None | N |
| Y/S | 0.6027 | likely_pathogenic | 0.5818 | pathogenic | -3.131 | Highly Destabilizing | 0.684 | D | 0.567 | neutral | N | 0.489570805 | None | None | N |
| Y/T | 0.7217 | likely_pathogenic | 0.7167 | pathogenic | -2.817 | Highly Destabilizing | 0.91 | D | 0.581 | neutral | None | None | None | None | N |
| Y/V | 0.4962 | ambiguous | 0.5187 | ambiguous | -1.713 | Destabilizing | 0.742 | D | 0.526 | neutral | None | None | None | None | N |
| Y/W | 0.5606 | ambiguous | 0.496 | ambiguous | -0.283 | Destabilizing | 0.996 | D | 0.535 | 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.