Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5742 | 17449;17450;17451 | chr2:178731542;178731541;178731540 | chr2:179596269;179596268;179596267 |
| N2AB | 5425 | 16498;16499;16500 | chr2:178731542;178731541;178731540 | chr2:179596269;179596268;179596267 |
| N2A | 4498 | 13717;13718;13719 | chr2:178731542;178731541;178731540 | chr2:179596269;179596268;179596267 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs72648943  |
-0.358 | 0.997 | N | 0.531 | 0.302 | None | gnomAD-2.1.1 | 3.08724E-04 | None | None | None | None | I | None | 8.28E-05 | 5.69E-05 | None | 0 | 0 | None | 0 | None | 3.22009E-04 | 5.65869E-04 | 2.83046E-04 |
| L/F | rs72648943 |
-0.358 | 0.997 | N | 0.531 | 0.302 | None | gnomAD-3.1.2 | 3.484E-04 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 4.70721E-04 | 0 | 6.6157E-04 | 0 | 4.78927E-04 |
| L/F | rs72648943 |
-0.358 | 0.997 | N | 0.531 | 0.302 | None | gnomAD-4.0.0 | 5.06665E-04 | None | None | None | None | I | None | 8.0156E-05 | 3.34012E-05 | None | 0 | 0 | None | 3.59768E-04 | 0 | 6.45358E-04 | 0 | 4.00641E-04 |
| L/P | rs750058681 |
-0.167 | 0.997 | N | 0.69 | 0.502 | 0.831918458575 | gnomAD-2.1.1 | 7.18E-06 | None | None | None | None | I | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/P | rs750058681 |
-0.167 | 0.997 | N | 0.69 | 0.502 | 0.831918458575 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs750058681 |
-0.167 | 0.997 | N | 0.69 | 0.502 | 0.831918458575 | gnomAD-4.0.0 | 3.72076E-06 | None | None | None | None | I | None | 8.01603E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3986 | ambiguous | 0.4454 | ambiguous | -0.652 | Destabilizing | 0.971 | D | 0.589 | neutral | None | None | None | None | I |
| L/C | 0.6913 | likely_pathogenic | 0.7041 | pathogenic | -0.717 | Destabilizing | 1.0 | D | 0.605 | neutral | None | None | None | None | I |
| L/D | 0.7969 | likely_pathogenic | 0.8338 | pathogenic | 0.412 | Stabilizing | 0.996 | D | 0.69 | prob.neutral | None | None | None | None | I |
| L/E | 0.4254 | ambiguous | 0.4654 | ambiguous | 0.355 | Stabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | I |
| L/F | 0.1543 | likely_benign | 0.1774 | benign | -0.474 | Destabilizing | 0.997 | D | 0.531 | neutral | N | 0.487124815 | None | None | I |
| L/G | 0.6915 | likely_pathogenic | 0.7417 | pathogenic | -0.847 | Destabilizing | 0.996 | D | 0.649 | neutral | None | None | None | None | I |
| L/H | 0.3375 | likely_benign | 0.3698 | ambiguous | -0.075 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | N | 0.486364346 | None | None | I |
| L/I | 0.1059 | likely_benign | 0.1113 | benign | -0.249 | Destabilizing | 0.4 | N | 0.299 | neutral | N | 0.509046534 | None | None | I |
| L/K | 0.3357 | likely_benign | 0.3622 | ambiguous | -0.239 | Destabilizing | 0.996 | D | 0.675 | neutral | None | None | None | None | I |
| L/M | 0.1533 | likely_benign | 0.1629 | benign | -0.375 | Destabilizing | 0.998 | D | 0.512 | neutral | None | None | None | None | I |
| L/N | 0.5429 | ambiguous | 0.5868 | pathogenic | -0.094 | Destabilizing | 0.996 | D | 0.69 | prob.neutral | None | None | None | None | I |
| L/P | 0.3712 | ambiguous | 0.4302 | ambiguous | -0.349 | Destabilizing | 0.997 | D | 0.69 | prob.neutral | N | 0.477339547 | None | None | I |
| L/Q | 0.1946 | likely_benign | 0.2154 | benign | -0.236 | Destabilizing | 0.998 | D | 0.686 | prob.neutral | None | None | None | None | I |
| L/R | 0.242 | likely_benign | 0.2623 | benign | 0.204 | Stabilizing | 0.997 | D | 0.681 | prob.neutral | N | 0.501272413 | None | None | I |
| L/S | 0.39 | ambiguous | 0.4542 | ambiguous | -0.691 | Destabilizing | 0.856 | D | 0.492 | neutral | None | None | None | None | I |
| L/T | 0.3206 | likely_benign | 0.3555 | ambiguous | -0.629 | Destabilizing | 0.971 | D | 0.591 | neutral | None | None | None | None | I |
| L/V | 0.1055 | likely_benign | 0.1122 | benign | -0.349 | Destabilizing | 0.4 | N | 0.323 | neutral | N | 0.453558611 | None | None | I |
| L/W | 0.3281 | likely_benign | 0.37 | ambiguous | -0.479 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | I |
| L/Y | 0.4484 | ambiguous | 0.4657 | ambiguous | -0.233 | Destabilizing | 0.999 | D | 0.575 | neutral | 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.