Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32159 | 96700;96701;96702 | chr2:178543498;178543497;178543496 | chr2:179408225;179408224;179408223 |
| N2AB | 30518 | 91777;91778;91779 | chr2:178543498;178543497;178543496 | chr2:179408225;179408224;179408223 |
| N2A | 29591 | 88996;88997;88998 | chr2:178543498;178543497;178543496 | chr2:179408225;179408224;179408223 |
| N2B | 23094 | 69505;69506;69507 | chr2:178543498;178543497;178543496 | chr2:179408225;179408224;179408223 |
| Novex-1 | 23219 | 69880;69881;69882 | chr2:178543498;178543497;178543496 | chr2:179408225;179408224;179408223 |
| Novex-2 | 23286 | 70081;70082;70083 | chr2:178543498;178543497;178543496 | chr2:179408225;179408224;179408223 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs1375895455  |
-0.862 | 1.0 | N | 0.87 | 0.621 | 0.80217922325 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| C/R | rs1375895455 |
-0.862 | 1.0 | N | 0.87 | 0.621 | 0.80217922325 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| C/R | rs1375895455 |
-0.862 | 1.0 | N | 0.87 | 0.621 | 0.80217922325 | gnomAD-4.0.0 | 7.68785E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43592E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.7769 | likely_pathogenic | 0.6816 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.561 | neutral | None | None | None | None | N |
| C/D | 0.9865 | likely_pathogenic | 0.9725 | pathogenic | -0.686 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| C/E | 0.991 | likely_pathogenic | 0.98 | pathogenic | -0.475 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| C/F | 0.7743 | likely_pathogenic | 0.6411 | pathogenic | -1.138 | Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.475127766 | None | None | N |
| C/G | 0.7108 | likely_pathogenic | 0.5657 | pathogenic | -2.094 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.493156283 | None | None | N |
| C/H | 0.9615 | likely_pathogenic | 0.927 | pathogenic | -2.22 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| C/I | 0.6793 | likely_pathogenic | 0.595 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| C/K | 0.9953 | likely_pathogenic | 0.9893 | pathogenic | -0.644 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| C/L | 0.7726 | likely_pathogenic | 0.6758 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.568 | neutral | None | None | None | None | N |
| C/M | 0.8587 | likely_pathogenic | 0.8022 | pathogenic | 0.13 | Stabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| C/N | 0.8848 | likely_pathogenic | 0.8206 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| C/P | 0.9849 | likely_pathogenic | 0.9789 | pathogenic | -1.051 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| C/Q | 0.9763 | likely_pathogenic | 0.9472 | pathogenic | -0.717 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| C/R | 0.9776 | likely_pathogenic | 0.949 | pathogenic | -1.031 | Destabilizing | 1.0 | D | 0.87 | deleterious | N | 0.474577426 | None | None | N |
| C/S | 0.7401 | likely_pathogenic | 0.6165 | pathogenic | -1.536 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.498679533 | None | None | N |
| C/T | 0.8075 | likely_pathogenic | 0.7014 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| C/V | 0.5498 | ambiguous | 0.4761 | ambiguous | -1.051 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | N |
| C/W | 0.9503 | likely_pathogenic | 0.9119 | pathogenic | -1.323 | Destabilizing | 1.0 | D | 0.831 | deleterious | N | 0.485977093 | None | None | N |
| C/Y | 0.8747 | likely_pathogenic | 0.7767 | pathogenic | -1.185 | Destabilizing | 1.0 | D | 0.847 | deleterious | N | 0.505434934 | 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.