Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27639 | 83140;83141;83142 | chr2:178563217;178563216;178563215 | chr2:179427944;179427943;179427942 |
| N2AB | 25998 | 78217;78218;78219 | chr2:178563217;178563216;178563215 | chr2:179427944;179427943;179427942 |
| N2A | 25071 | 75436;75437;75438 | chr2:178563217;178563216;178563215 | chr2:179427944;179427943;179427942 |
| N2B | 18574 | 55945;55946;55947 | chr2:178563217;178563216;178563215 | chr2:179427944;179427943;179427942 |
| Novex-1 | 18699 | 56320;56321;56322 | chr2:178563217;178563216;178563215 | chr2:179427944;179427943;179427942 |
| Novex-2 | 18766 | 56521;56522;56523 | chr2:178563217;178563216;178563215 | chr2:179427944;179427943;179427942 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs748142048  |
0.116 | 0.998 | N | 0.623 | 0.457 | 0.202949470691 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/D | rs748142048 |
0.116 | 0.998 | N | 0.623 | 0.457 | 0.202949470691 | gnomAD-4.0.0 | 3.18279E-06 | None | None | None | None | N | None | 0 | 4.57289E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/K | rs781086219 |
0.226 | 0.767 | N | 0.435 | 0.146 | 0.0666544352282 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/K | rs781086219 |
0.226 | 0.767 | N | 0.435 | 0.146 | 0.0666544352282 | gnomAD-4.0.0 | 6.84239E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15931E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3371 | likely_benign | 0.3368 | benign | -0.389 | Destabilizing | 0.997 | D | 0.658 | neutral | None | None | None | None | N |
| N/C | 0.4363 | ambiguous | 0.4253 | ambiguous | 0.311 | Stabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| N/D | 0.1597 | likely_benign | 0.146 | benign | -0.134 | Destabilizing | 0.998 | D | 0.623 | neutral | N | 0.50166391 | None | None | N |
| N/E | 0.4067 | ambiguous | 0.3921 | ambiguous | -0.16 | Destabilizing | 0.997 | D | 0.645 | neutral | None | None | None | None | N |
| N/F | 0.6208 | likely_pathogenic | 0.627 | pathogenic | -0.644 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| N/G | 0.2383 | likely_benign | 0.2558 | benign | -0.585 | Destabilizing | 0.998 | D | 0.585 | neutral | None | None | None | None | N |
| N/H | 0.1444 | likely_benign | 0.1382 | benign | -0.584 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.492756425 | None | None | N |
| N/I | 0.4723 | ambiguous | 0.4377 | ambiguous | 0.049 | Stabilizing | 1.0 | D | 0.797 | deleterious | N | 0.51617535 | None | None | N |
| N/K | 0.2546 | likely_benign | 0.2289 | benign | -0.005 | Destabilizing | 0.767 | D | 0.435 | neutral | N | 0.471111716 | None | None | N |
| N/L | 0.4025 | ambiguous | 0.3906 | ambiguous | 0.049 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| N/M | 0.3953 | ambiguous | 0.3886 | ambiguous | 0.452 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| N/P | 0.8789 | likely_pathogenic | 0.8769 | pathogenic | -0.07 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | N |
| N/Q | 0.3358 | likely_benign | 0.3305 | benign | -0.508 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| N/R | 0.3858 | ambiguous | 0.3701 | ambiguous | 0.099 | Stabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| N/S | 0.1576 | likely_benign | 0.1529 | benign | -0.243 | Destabilizing | 0.996 | D | 0.549 | neutral | N | 0.516478647 | None | None | N |
| N/T | 0.2392 | likely_benign | 0.2284 | benign | -0.128 | Destabilizing | 0.998 | D | 0.661 | neutral | N | 0.49270227 | None | None | N |
| N/V | 0.478 | ambiguous | 0.4551 | ambiguous | -0.07 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| N/W | 0.8188 | likely_pathogenic | 0.8153 | pathogenic | -0.575 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| N/Y | 0.2227 | likely_benign | 0.2101 | benign | -0.337 | Destabilizing | 1.0 | D | 0.771 | deleterious | N | 0.520404386 | 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.