Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15407 | 46444;46445;46446 | chr2:178620302;178620301;178620300 | chr2:179485029;179485028;179485027 |
| N2AB | 13766 | 41521;41522;41523 | chr2:178620302;178620301;178620300 | chr2:179485029;179485028;179485027 |
| N2A | 12839 | 38740;38741;38742 | chr2:178620302;178620301;178620300 | chr2:179485029;179485028;179485027 |
| N2B | 6342 | 19249;19250;19251 | chr2:178620302;178620301;178620300 | chr2:179485029;179485028;179485027 |
| Novex-1 | 6467 | 19624;19625;19626 | chr2:178620302;178620301;178620300 | chr2:179485029;179485028;179485027 |
| Novex-2 | 6534 | 19825;19826;19827 | chr2:178620302;178620301;178620300 | chr2:179485029;179485028;179485027 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs370808856  |
-0.235 | 0.893 | N | 0.308 | 0.147 | 0.341934017632 | gnomAD-2.1.1 | 4.63E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 4.57E-05 | None | 0 | 0 | 0 |
| D/E | rs370808856 |
-0.235 | 0.893 | N | 0.308 | 0.147 | 0.341934017632 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| D/E | rs370808856 |
-0.235 | 0.893 | N | 0.308 | 0.147 | 0.341934017632 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| D/E | rs370808856 |
-0.235 | 0.893 | N | 0.308 | 0.147 | 0.341934017632 | gnomAD-4.0.0 | 1.27475E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.21717E-05 | 1.6547E-05 |
| D/G | rs375445028 |
-0.589 | 0.998 | D | 0.71 | 0.572 | 0.49530441419 | gnomAD-2.1.1 | 9.22E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.15274E-04 | None | 0 | None | 0 | 0 | 0 |
| D/G | rs375445028 |
-0.589 | 0.998 | D | 0.71 | 0.572 | 0.49530441419 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.94477E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/G | rs375445028 |
-0.589 | 0.998 | D | 0.71 | 0.572 | 0.49530441419 | gnomAD-4.0.0 | 1.22081E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.22808E-04 | None | 0 | 0 | 5.04938E-06 | 3.03389E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.531 | ambiguous | 0.6292 | pathogenic | -0.385 | Destabilizing | 0.999 | D | 0.666 | neutral | N | 0.506409916 | None | None | N |
| D/C | 0.9389 | likely_pathogenic | 0.9609 | pathogenic | -0.065 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| D/E | 0.4839 | ambiguous | 0.5693 | pathogenic | -0.575 | Destabilizing | 0.893 | D | 0.308 | neutral | N | 0.50514469 | None | None | N |
| D/F | 0.9415 | likely_pathogenic | 0.9564 | pathogenic | -0.285 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| D/G | 0.6493 | likely_pathogenic | 0.735 | pathogenic | -0.665 | Destabilizing | 0.998 | D | 0.71 | prob.delet. | D | 0.6685752 | None | None | N |
| D/H | 0.7448 | likely_pathogenic | 0.7804 | pathogenic | -0.547 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.589988995 | None | None | N |
| D/I | 0.8509 | likely_pathogenic | 0.8955 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| D/K | 0.8601 | likely_pathogenic | 0.8855 | pathogenic | -0.214 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| D/L | 0.8683 | likely_pathogenic | 0.905 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| D/M | 0.9372 | likely_pathogenic | 0.9531 | pathogenic | 0.686 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/N | 0.2234 | likely_benign | 0.2448 | benign | -0.491 | Destabilizing | 0.999 | D | 0.625 | neutral | N | 0.509930083 | None | None | N |
| D/P | 0.8844 | likely_pathogenic | 0.9248 | pathogenic | 0.114 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/Q | 0.829 | likely_pathogenic | 0.8656 | pathogenic | -0.4 | Destabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/R | 0.8838 | likely_pathogenic | 0.9111 | pathogenic | -0.097 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| D/S | 0.3221 | likely_benign | 0.3598 | ambiguous | -0.664 | Destabilizing | 0.997 | D | 0.613 | neutral | None | None | None | None | N |
| D/T | 0.5391 | ambiguous | 0.5605 | ambiguous | -0.448 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| D/V | 0.6722 | likely_pathogenic | 0.7518 | pathogenic | 0.114 | Stabilizing | 0.999 | D | 0.757 | deleterious | D | 0.544891379 | None | None | N |
| D/W | 0.9872 | likely_pathogenic | 0.9902 | pathogenic | -0.192 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| D/Y | 0.6924 | likely_pathogenic | 0.7527 | pathogenic | -0.083 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.631216984 | 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.