Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18247 | 54964;54965;54966 | chr2:178603948;178603947;178603946 | chr2:179468675;179468674;179468673 |
| N2AB | 16606 | 50041;50042;50043 | chr2:178603948;178603947;178603946 | chr2:179468675;179468674;179468673 |
| N2A | 15679 | 47260;47261;47262 | chr2:178603948;178603947;178603946 | chr2:179468675;179468674;179468673 |
| N2B | 9182 | 27769;27770;27771 | chr2:178603948;178603947;178603946 | chr2:179468675;179468674;179468673 |
| Novex-1 | 9307 | 28144;28145;28146 | chr2:178603948;178603947;178603946 | chr2:179468675;179468674;179468673 |
| Novex-2 | 9374 | 28345;28346;28347 | chr2:178603948;178603947;178603946 | chr2:179468675;179468674;179468673 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs368858337  |
-0.661 | 0.042 | N | 0.668 | 0.197 | 0.359963025489 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| M/I | rs368858337 |
-0.661 | 0.042 | N | 0.668 | 0.197 | 0.359963025489 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/I | rs368858337 |
-0.661 | 0.042 | N | 0.668 | 0.197 | 0.359963025489 | gnomAD-4.0.0 | 1.61261E-05 | None | None | None | None | N | None | 1.73555E-04 | 0 | None | 0 | 0 | None | 0 | 4.96196E-04 | 3.39314E-06 | 1.09941E-05 | 8.01179E-05 |
| M/T | rs200585270 |
-1.839 | 0.042 | N | 0.659 | 0.259 | None | gnomAD-2.1.1 | 2.93098E-04 | None | None | None | None | N | None | 8.28E-05 | 1.24568E-03 | None | 7.75044E-04 | 0 | None | 0 | None | 0 | 1.25113E-04 | 1.68681E-03 |
| M/T | rs200585270 |
-1.839 | 0.042 | N | 0.659 | 0.259 | None | gnomAD-3.1.2 | 1.51348E-04 | None | None | None | None | N | None | 7.24E-05 | 5.90319E-04 | 0 | 5.76369E-04 | 0 | None | 0 | 0 | 1.03056E-04 | 0 | 9.56023E-04 |
| M/T | rs200585270 |
-1.839 | 0.042 | N | 0.659 | 0.259 | None | gnomAD-4.0.0 | 1.27761E-04 | None | None | None | None | N | None | 6.67236E-05 | 9.67344E-04 | None | 8.79686E-04 | 0 | None | 0 | 1.32319E-03 | 7.0407E-05 | 0 | 4.1656E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4376 | ambiguous | 0.4075 | ambiguous | -2.734 | Highly Destabilizing | 0.002 | N | 0.426 | neutral | None | None | None | None | N |
| M/C | 0.6344 | likely_pathogenic | 0.6527 | pathogenic | -2.425 | Highly Destabilizing | 0.859 | D | 0.691 | prob.neutral | None | None | None | None | N |
| M/D | 0.976 | likely_pathogenic | 0.9735 | pathogenic | -2.543 | Highly Destabilizing | 0.22 | N | 0.721 | prob.delet. | None | None | None | None | N |
| M/E | 0.8109 | likely_pathogenic | 0.804 | pathogenic | -2.368 | Highly Destabilizing | 0.22 | N | 0.671 | neutral | None | None | None | None | N |
| M/F | 0.4154 | ambiguous | 0.3857 | ambiguous | -1.145 | Destabilizing | 0.124 | N | 0.678 | prob.neutral | None | None | None | None | N |
| M/G | 0.807 | likely_pathogenic | 0.7713 | pathogenic | -3.117 | Highly Destabilizing | 0.22 | N | 0.693 | prob.neutral | None | None | None | None | N |
| M/H | 0.7441 | likely_pathogenic | 0.7311 | pathogenic | -2.607 | Highly Destabilizing | 0.859 | D | 0.695 | prob.neutral | None | None | None | None | N |
| M/I | 0.7118 | likely_pathogenic | 0.6714 | pathogenic | -1.625 | Destabilizing | 0.042 | N | 0.668 | neutral | N | 0.417295874 | None | None | N |
| M/K | 0.51 | ambiguous | 0.4732 | ambiguous | -2.026 | Highly Destabilizing | 0.175 | N | 0.683 | prob.neutral | N | 0.421738902 | None | None | N |
| M/L | 0.3122 | likely_benign | 0.2662 | benign | -1.625 | Destabilizing | None | N | 0.267 | neutral | N | 0.436785712 | None | None | N |
| M/N | 0.7951 | likely_pathogenic | 0.8031 | pathogenic | -2.198 | Highly Destabilizing | 0.497 | N | 0.707 | prob.neutral | None | None | None | None | N |
| M/P | 0.9975 | likely_pathogenic | 0.9968 | pathogenic | -1.982 | Destabilizing | 0.667 | D | 0.707 | prob.neutral | None | None | None | None | N |
| M/Q | 0.4169 | ambiguous | 0.4303 | ambiguous | -2.001 | Highly Destabilizing | 0.667 | D | 0.681 | prob.neutral | None | None | None | None | N |
| M/R | 0.5554 | ambiguous | 0.4773 | ambiguous | -1.857 | Destabilizing | 0.301 | N | 0.715 | prob.delet. | N | 0.392474787 | None | None | N |
| M/S | 0.4427 | ambiguous | 0.4338 | ambiguous | -2.72 | Highly Destabilizing | 0.011 | N | 0.446 | neutral | None | None | None | None | N |
| M/T | 0.3449 | ambiguous | 0.3088 | benign | -2.456 | Highly Destabilizing | 0.042 | N | 0.659 | neutral | N | 0.388050403 | None | None | N |
| M/V | 0.1931 | likely_benign | 0.1656 | benign | -1.982 | Destabilizing | 0.042 | N | 0.591 | neutral | N | 0.417853235 | None | None | N |
| M/W | 0.8654 | likely_pathogenic | 0.8182 | pathogenic | -1.434 | Destabilizing | 0.958 | D | 0.678 | prob.neutral | None | None | None | None | N |
| M/Y | 0.7445 | likely_pathogenic | 0.6972 | pathogenic | -1.533 | Destabilizing | 0.667 | D | 0.718 | prob.delet. | 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.