Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18402 | 55429;55430;55431 | chr2:178602067;178602066;178602065 | chr2:179466794;179466793;179466792 |
| N2AB | 16761 | 50506;50507;50508 | chr2:178602067;178602066;178602065 | chr2:179466794;179466793;179466792 |
| N2A | 15834 | 47725;47726;47727 | chr2:178602067;178602066;178602065 | chr2:179466794;179466793;179466792 |
| N2B | 9337 | 28234;28235;28236 | chr2:178602067;178602066;178602065 | chr2:179466794;179466793;179466792 |
| Novex-1 | 9462 | 28609;28610;28611 | chr2:178602067;178602066;178602065 | chr2:179466794;179466793;179466792 |
| Novex-2 | 9529 | 28810;28811;28812 | chr2:178602067;178602066;178602065 | chr2:179466794;179466793;179466792 |
| 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/L | None | None | 0.993 | N | 0.43 | 0.453 | 0.618312362157 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/N | rs776899398  |
-0.193 | 1.0 | N | 0.844 | 0.686 | 0.903074480649 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| I/N | rs776899398 |
-0.193 | 1.0 | N | 0.844 | 0.686 | 0.903074480649 | gnomAD-4.0.0 | 6.84591E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99847E-07 | 0 | 0 |
| I/S | rs776899398 |
-0.708 | 1.0 | N | 0.813 | 0.643 | 0.904873369186 | gnomAD-2.1.1 | 4.84E-05 | None | None | None | None | I | None | 0 | 2.90309E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/S | rs776899398 |
-0.708 | 1.0 | N | 0.813 | 0.643 | 0.904873369186 | gnomAD-3.1.2 | 1.64573E-04 | None | None | None | None | I | None | 0 | 1.50978E-03 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| I/S | rs776899398 |
-0.708 | 1.0 | N | 0.813 | 0.643 | 0.904873369186 | gnomAD-4.0.0 | 3.10052E-05 | None | None | None | None | I | None | 0 | 5.34135E-04 | None | 0 | 0 | None | 0 | 0 | 1.44162E-05 | 0 | 1.60251E-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 | 0.9302 | likely_pathogenic | 0.9494 | pathogenic | -1.35 | Destabilizing | 0.999 | D | 0.651 | neutral | None | None | None | None | I |
| I/C | 0.903 | likely_pathogenic | 0.9335 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| I/D | 0.9963 | likely_pathogenic | 0.9978 | pathogenic | -0.537 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| I/E | 0.9837 | likely_pathogenic | 0.9879 | pathogenic | -0.579 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| I/F | 0.2957 | likely_benign | 0.3796 | ambiguous | -1.151 | Destabilizing | 1.0 | D | 0.802 | deleterious | D | 0.529176664 | None | None | I |
| I/G | 0.9826 | likely_pathogenic | 0.9881 | pathogenic | -1.607 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | I |
| I/H | 0.9566 | likely_pathogenic | 0.9726 | pathogenic | -0.888 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | I |
| I/K | 0.9285 | likely_pathogenic | 0.9507 | pathogenic | -0.655 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| I/L | 0.2048 | likely_benign | 0.2318 | benign | -0.75 | Destabilizing | 0.993 | D | 0.43 | neutral | N | 0.493738315 | None | None | I |
| I/M | 0.1844 | likely_benign | 0.2107 | benign | -0.589 | Destabilizing | 1.0 | D | 0.785 | deleterious | N | 0.500032192 | None | None | I |
| I/N | 0.944 | likely_pathogenic | 0.9552 | pathogenic | -0.403 | Destabilizing | 1.0 | D | 0.844 | deleterious | N | 0.518643426 | None | None | I |
| I/P | 0.9902 | likely_pathogenic | 0.9944 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| I/Q | 0.9329 | likely_pathogenic | 0.9507 | pathogenic | -0.647 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | I |
| I/R | 0.8997 | likely_pathogenic | 0.9313 | pathogenic | -0.13 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| I/S | 0.9372 | likely_pathogenic | 0.9513 | pathogenic | -1.023 | Destabilizing | 1.0 | D | 0.813 | deleterious | N | 0.500285681 | None | None | I |
| I/T | 0.8736 | likely_pathogenic | 0.8903 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.50534811 | None | None | I |
| I/V | 0.1407 | likely_benign | 0.1524 | benign | -0.918 | Destabilizing | 0.993 | D | 0.359 | neutral | N | 0.471501292 | None | None | I |
| I/W | 0.8987 | likely_pathogenic | 0.9386 | pathogenic | -1.137 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| I/Y | 0.8266 | likely_pathogenic | 0.8768 | pathogenic | -0.884 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
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.