Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23902 | 71929;71930;71931 | chr2:178574428;178574427;178574426 | chr2:179439155;179439154;179439153 |
| N2AB | 22261 | 67006;67007;67008 | chr2:178574428;178574427;178574426 | chr2:179439155;179439154;179439153 |
| N2A | 21334 | 64225;64226;64227 | chr2:178574428;178574427;178574426 | chr2:179439155;179439154;179439153 |
| N2B | 14837 | 44734;44735;44736 | chr2:178574428;178574427;178574426 | chr2:179439155;179439154;179439153 |
| Novex-1 | 14962 | 45109;45110;45111 | chr2:178574428;178574427;178574426 | chr2:179439155;179439154;179439153 |
| Novex-2 | 15029 | 45310;45311;45312 | chr2:178574428;178574427;178574426 | chr2:179439155;179439154;179439153 |
| 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 | rs55837610  |
-2.883 | 0.166 | N | 0.698 | 0.275 | None | gnomAD-2.1.1 | 2.16956E-03 | None | None | None | None | N | None | 6.20142E-04 | 1.89683E-03 | None | 4.26191E-03 | 0 | None | 0 | None | 2.80426E-04 | 3.49771E-03 | 3.80175E-03 |
| I/T | rs55837610 |
-2.883 | 0.166 | N | 0.698 | 0.275 | None | gnomAD-3.1.2 | 2.01189E-03 | None | None | None | None | N | None | 7.23973E-04 | 1.11417E-03 | 0 | 4.61361E-03 | 0 | None | 7.53154E-04 | 6.32911E-03 | 3.32353E-03 | 0 | 3.34928E-03 |
| I/T | rs55837610 |
-2.883 | 0.166 | N | 0.698 | 0.275 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 2E-03 | None | None | None | 0 | None |
| I/T | rs55837610 |
-2.883 | 0.166 | N | 0.698 | 0.275 | None | gnomAD-4.0.0 | 2.89115E-03 | None | None | None | None | N | None | 6.66489E-04 | 1.88352E-03 | None | 4.02299E-03 | 0 | None | 6.71938E-04 | 2.31328E-03 | 3.51893E-03 | 1.09823E-05 | 2.78525E-03 |
| I/V | rs1160675688 |
-1.961 | 0.001 | N | 0.171 | 0.074 | 0.28492961333 | 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 |
| I/V | rs1160675688 |
-1.961 | 0.001 | N | 0.171 | 0.074 | 0.28492961333 | gnomAD-4.0.0 | 2.05294E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47907E-05 | 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 | 0.1991 | likely_benign | 0.2158 | benign | -2.786 | Highly Destabilizing | 0.209 | N | 0.678 | prob.neutral | None | None | None | None | N |
| I/C | 0.5523 | ambiguous | 0.5701 | pathogenic | -2.133 | Highly Destabilizing | 0.991 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/D | 0.8143 | likely_pathogenic | 0.8575 | pathogenic | -3.473 | Highly Destabilizing | 0.561 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/E | 0.6462 | likely_pathogenic | 0.6965 | pathogenic | -3.309 | Highly Destabilizing | 0.561 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/F | 0.1154 | likely_benign | 0.1252 | benign | -1.551 | Destabilizing | 0.326 | N | 0.689 | prob.neutral | N | 0.419933534 | None | None | N |
| I/G | 0.6035 | likely_pathogenic | 0.661 | pathogenic | -3.219 | Highly Destabilizing | 0.39 | N | 0.721 | prob.delet. | None | None | None | None | N |
| I/H | 0.4874 | ambiguous | 0.5156 | ambiguous | -2.571 | Highly Destabilizing | 0.818 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/K | 0.527 | ambiguous | 0.5533 | ambiguous | -2.222 | Highly Destabilizing | 0.561 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/L | 0.1064 | likely_benign | 0.1087 | benign | -1.529 | Destabilizing | 0.08 | N | 0.456 | neutral | N | 0.457489058 | None | None | N |
| I/M | 0.0751 | likely_benign | 0.0759 | benign | -1.533 | Destabilizing | 0.873 | D | 0.736 | prob.delet. | N | 0.472978586 | None | None | N |
| I/N | 0.3418 | ambiguous | 0.3934 | ambiguous | -2.481 | Highly Destabilizing | 0.772 | D | 0.743 | deleterious | N | 0.471190974 | None | None | N |
| I/P | 0.9626 | likely_pathogenic | 0.9738 | pathogenic | -1.934 | Destabilizing | 0.901 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/Q | 0.4863 | ambiguous | 0.5053 | ambiguous | -2.42 | Highly Destabilizing | 0.901 | D | 0.746 | deleterious | None | None | None | None | N |
| I/R | 0.369 | ambiguous | 0.3974 | ambiguous | -1.759 | Destabilizing | 0.818 | D | 0.747 | deleterious | None | None | None | None | N |
| I/S | 0.1906 | likely_benign | 0.2085 | benign | -3.012 | Highly Destabilizing | 0.005 | N | 0.517 | neutral | N | 0.407022952 | None | None | N |
| I/T | 0.0983 | likely_benign | 0.1077 | benign | -2.744 | Highly Destabilizing | 0.166 | N | 0.698 | prob.neutral | N | 0.427339509 | None | None | N |
| I/V | 0.069 | likely_benign | 0.0772 | benign | -1.934 | Destabilizing | 0.001 | N | 0.171 | neutral | N | 0.435862992 | None | None | N |
| I/W | 0.6743 | likely_pathogenic | 0.6781 | pathogenic | -1.966 | Destabilizing | 0.972 | D | 0.723 | prob.delet. | None | None | None | None | N |
| I/Y | 0.4172 | ambiguous | 0.4185 | ambiguous | -1.828 | Destabilizing | 0.004 | N | 0.593 | 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.