Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27899 | 83920;83921;83922 | chr2:178562437;178562436;178562435 | chr2:179427164;179427163;179427162 |
| N2AB | 26258 | 78997;78998;78999 | chr2:178562437;178562436;178562435 | chr2:179427164;179427163;179427162 |
| N2A | 25331 | 76216;76217;76218 | chr2:178562437;178562436;178562435 | chr2:179427164;179427163;179427162 |
| N2B | 18834 | 56725;56726;56727 | chr2:178562437;178562436;178562435 | chr2:179427164;179427163;179427162 |
| Novex-1 | 18959 | 57100;57101;57102 | chr2:178562437;178562436;178562435 | chr2:179427164;179427163;179427162 |
| Novex-2 | 19026 | 57301;57302;57303 | chr2:178562437;178562436;178562435 | chr2:179427164;179427163;179427162 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs775678192  |
-0.734 | 0.164 | N | 0.39 | 0.064 | 0.483962474653 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 1.29282E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs775678192 |
-0.734 | 0.164 | N | 0.39 | 0.064 | 0.483962474653 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs775678192 |
-0.734 | 0.164 | N | 0.39 | 0.064 | 0.483962474653 | gnomAD-4.0.0 | 2.47947E-06 | None | None | None | None | N | None | 5.34045E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1846 | likely_benign | 0.2251 | benign | -2.012 | Highly Destabilizing | 0.309 | N | 0.513 | neutral | N | 0.510014034 | None | None | N |
| V/C | 0.5851 | likely_pathogenic | 0.6258 | pathogenic | -1.615 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| V/D | 0.3632 | ambiguous | 0.4567 | ambiguous | -2.568 | Highly Destabilizing | 0.91 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/E | 0.2793 | likely_benign | 0.3557 | ambiguous | -2.444 | Highly Destabilizing | 0.684 | D | 0.699 | prob.neutral | N | 0.497543382 | None | None | N |
| V/F | 0.1401 | likely_benign | 0.1677 | benign | -1.25 | Destabilizing | 0.91 | D | 0.71 | prob.delet. | None | None | None | None | N |
| V/G | 0.3692 | ambiguous | 0.4391 | ambiguous | -2.451 | Highly Destabilizing | 0.684 | D | 0.735 | prob.delet. | N | 0.493916811 | None | None | N |
| V/H | 0.4351 | ambiguous | 0.5215 | ambiguous | -2.036 | Highly Destabilizing | 0.996 | D | 0.648 | neutral | None | None | None | None | N |
| V/I | 0.0656 | likely_benign | 0.0637 | benign | -0.831 | Destabilizing | 0.001 | N | 0.166 | neutral | None | None | None | None | N |
| V/K | 0.4263 | ambiguous | 0.539 | ambiguous | -1.701 | Destabilizing | 0.742 | D | 0.685 | prob.neutral | None | None | None | None | N |
| V/L | 0.13 | likely_benign | 0.1386 | benign | -0.831 | Destabilizing | 0.164 | N | 0.39 | neutral | N | 0.490985556 | None | None | N |
| V/M | 0.1073 | likely_benign | 0.1156 | benign | -0.879 | Destabilizing | 0.164 | N | 0.374 | neutral | N | 0.46668475 | None | None | N |
| V/N | 0.2825 | likely_benign | 0.3221 | benign | -1.801 | Destabilizing | 0.91 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/P | 0.9642 | likely_pathogenic | 0.9752 | pathogenic | -1.196 | Destabilizing | 0.953 | D | 0.678 | prob.neutral | None | None | None | None | N |
| V/Q | 0.3181 | likely_benign | 0.3842 | ambiguous | -1.823 | Destabilizing | 0.953 | D | 0.657 | neutral | None | None | None | None | N |
| V/R | 0.3318 | likely_benign | 0.4452 | ambiguous | -1.311 | Destabilizing | 0.91 | D | 0.698 | prob.neutral | None | None | None | None | N |
| V/S | 0.2081 | likely_benign | 0.2522 | benign | -2.357 | Highly Destabilizing | 0.59 | D | 0.695 | prob.neutral | None | None | None | None | N |
| V/T | 0.1363 | likely_benign | 0.1543 | benign | -2.116 | Highly Destabilizing | 0.009 | N | 0.245 | neutral | None | None | None | None | N |
| V/W | 0.6323 | likely_pathogenic | 0.7194 | pathogenic | -1.641 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | N |
| V/Y | 0.3989 | ambiguous | 0.462 | ambiguous | -1.32 | Destabilizing | 0.984 | D | 0.691 | prob.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.