Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16191 | 48796;48797;48798 | chr2:178615374;178615373;178615372 | chr2:179480101;179480100;179480099 |
| N2AB | 14550 | 43873;43874;43875 | chr2:178615374;178615373;178615372 | chr2:179480101;179480100;179480099 |
| N2A | 13623 | 41092;41093;41094 | chr2:178615374;178615373;178615372 | chr2:179480101;179480100;179480099 |
| N2B | 7126 | 21601;21602;21603 | chr2:178615374;178615373;178615372 | chr2:179480101;179480100;179480099 |
| Novex-1 | 7251 | 21976;21977;21978 | chr2:178615374;178615373;178615372 | chr2:179480101;179480100;179480099 |
| Novex-2 | 7318 | 22177;22178;22179 | chr2:178615374;178615373;178615372 | chr2:179480101;179480100;179480099 |
| 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 | None | None | 0.002 | D | 0.403 | 0.11 | 0.364141725642 | gnomAD-4.0.0 | 4.78124E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.59013E-06 | 0 | 0 |
| I/T | rs372753303  |
-2.447 | 0.055 | N | 0.581 | 0.114 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| I/T | rs372753303 |
-2.447 | 0.055 | N | 0.581 | 0.114 | None | gnomAD-4.0.0 | 4.79266E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39984E-06 | 0 | 1.65821E-05 |
| I/V | rs747433688 |
-1.36 | 0.005 | N | 0.385 | 0.051 | 0.281780670237 | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.83E-05 | 1.40687E-04 |
| I/V | rs747433688 |
-1.36 | 0.005 | N | 0.385 | 0.051 | 0.281780670237 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 4.77555E-04 |
| I/V | rs747433688 |
-1.36 | 0.005 | N | 0.385 | 0.051 | 0.281780670237 | gnomAD-4.0.0 | 6.63561E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56187E-05 | 0 | 8.73571E-05 | 0 | 4.80769E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3638 | ambiguous | 0.3136 | benign | -2.481 | Highly Destabilizing | 0.016 | N | 0.558 | neutral | None | None | None | None | N |
| I/C | 0.6603 | likely_pathogenic | 0.6511 | pathogenic | -1.775 | Destabilizing | 0.864 | D | 0.613 | neutral | None | None | None | None | N |
| I/D | 0.8459 | likely_pathogenic | 0.813 | pathogenic | -2.506 | Highly Destabilizing | 0.038 | N | 0.583 | neutral | None | None | None | None | N |
| I/E | 0.6555 | likely_pathogenic | 0.5997 | pathogenic | -2.377 | Highly Destabilizing | 0.072 | N | 0.581 | neutral | None | None | None | None | N |
| I/F | 0.1989 | likely_benign | 0.1922 | benign | -1.548 | Destabilizing | 0.038 | N | 0.615 | neutral | None | None | None | None | N |
| I/G | 0.8162 | likely_pathogenic | 0.7671 | pathogenic | -2.943 | Highly Destabilizing | 0.072 | N | 0.581 | neutral | None | None | None | None | N |
| I/H | 0.4722 | ambiguous | 0.4817 | ambiguous | -2.216 | Highly Destabilizing | 0.356 | N | 0.623 | neutral | None | None | None | None | N |
| I/K | 0.5304 | ambiguous | 0.4954 | ambiguous | -1.977 | Destabilizing | 0.055 | N | 0.575 | neutral | D | 0.540541053 | None | None | N |
| I/L | 0.101 | likely_benign | 0.0968 | benign | -1.193 | Destabilizing | None | N | 0.234 | neutral | N | 0.474624262 | None | None | N |
| I/M | 0.1031 | likely_benign | 0.1029 | benign | -1.05 | Destabilizing | 0.002 | N | 0.403 | neutral | D | 0.62034108 | None | None | N |
| I/N | 0.3573 | ambiguous | 0.3765 | ambiguous | -2.055 | Highly Destabilizing | None | N | 0.561 | neutral | None | None | None | None | N |
| I/P | 0.9893 | likely_pathogenic | 0.981 | pathogenic | -1.598 | Destabilizing | 0.628 | D | 0.623 | neutral | None | None | None | None | N |
| I/Q | 0.4659 | ambiguous | 0.4433 | ambiguous | -2.086 | Highly Destabilizing | 0.214 | N | 0.621 | neutral | None | None | None | None | N |
| I/R | 0.4153 | ambiguous | 0.3758 | ambiguous | -1.452 | Destabilizing | 0.171 | N | 0.623 | neutral | N | 0.509297694 | None | None | N |
| I/S | 0.3578 | ambiguous | 0.3338 | benign | -2.738 | Highly Destabilizing | 0.072 | N | 0.577 | neutral | None | None | None | None | N |
| I/T | 0.1878 | likely_benign | 0.1735 | benign | -2.481 | Highly Destabilizing | 0.055 | N | 0.581 | neutral | N | 0.502591456 | None | None | N |
| I/V | 0.083 | likely_benign | 0.0806 | benign | -1.598 | Destabilizing | 0.005 | N | 0.385 | neutral | N | 0.479400004 | None | None | N |
| I/W | 0.7865 | likely_pathogenic | 0.7611 | pathogenic | -1.804 | Destabilizing | 0.864 | D | 0.647 | neutral | None | None | None | None | N |
| I/Y | 0.4814 | ambiguous | 0.4977 | ambiguous | -1.577 | Destabilizing | 0.356 | N | 0.616 | 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.