Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5438 | 16537;16538;16539 | chr2:178732864;178732863;178732862 | chr2:179597591;179597590;179597589 |
| N2AB | 5121 | 15586;15587;15588 | chr2:178732864;178732863;178732862 | chr2:179597591;179597590;179597589 |
| N2A | 4194 | 12805;12806;12807 | chr2:178732864;178732863;178732862 | chr2:179597591;179597590;179597589 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | None | None | 0.961 | N | 0.541 | 0.314 | 0.423480098753 | gnomAD-4.0.0 | 1.59333E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.78009E-05 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs190636272  |
-0.09 | 0.98 | N | 0.554 | 0.237 | None | gnomAD-2.1.1 | 5.7671E-04 | None | None | None | None | I | None | 8.27E-05 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 3.20847E-04 | 1.13781E-03 | 5.6338E-04 |
| K/R | rs190636272 |
-0.09 | 0.98 | N | 0.554 | 0.237 | None | gnomAD-3.1.2 | 5.97984E-04 | None | None | None | None | I | None | 7.24E-05 | 6.55E-05 | 0 | 0 | 0 | None | 9.42E-05 | 0 | 1.22005E-03 | 4.14079E-04 | 4.78011E-04 |
| K/R | rs190636272 |
-0.09 | 0.98 | N | 0.554 | 0.237 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| K/R | rs190636272 |
-0.09 | 0.98 | N | 0.554 | 0.237 | None | gnomAD-4.0.0 | 8.02846E-04 | None | None | None | None | I | None | 1.19949E-04 | 6.66933E-05 | None | 0 | 0 | None | 2.18791E-04 | 0 | 1.04133E-03 | 4.3958E-05 | 5.76461E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3079 | likely_benign | 0.3394 | benign | -0.468 | Destabilizing | 0.304 | N | 0.332 | neutral | None | None | None | None | I |
| K/C | 0.7366 | likely_pathogenic | 0.7707 | pathogenic | -0.475 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| K/D | 0.5904 | likely_pathogenic | 0.6224 | pathogenic | 0.215 | Stabilizing | 0.991 | D | 0.691 | prob.neutral | None | None | None | None | I |
| K/E | 0.1545 | likely_benign | 0.1772 | benign | 0.305 | Stabilizing | 0.961 | D | 0.541 | neutral | N | 0.439127876 | None | None | I |
| K/F | 0.844 | likely_pathogenic | 0.8773 | pathogenic | -0.233 | Destabilizing | 0.999 | D | 0.79 | deleterious | None | None | None | None | I |
| K/G | 0.4862 | ambiguous | 0.5174 | ambiguous | -0.798 | Destabilizing | 0.97 | D | 0.673 | neutral | None | None | None | None | I |
| K/H | 0.3938 | ambiguous | 0.4273 | ambiguous | -1.058 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| K/I | 0.4354 | ambiguous | 0.4952 | ambiguous | 0.368 | Stabilizing | 0.994 | D | 0.781 | deleterious | N | 0.410693268 | None | None | I |
| K/L | 0.4472 | ambiguous | 0.4966 | ambiguous | 0.368 | Stabilizing | 0.97 | D | 0.709 | prob.delet. | None | None | None | None | I |
| K/M | 0.2793 | likely_benign | 0.3154 | benign | 0.165 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | None | None | None | None | I |
| K/N | 0.4897 | ambiguous | 0.534 | ambiguous | -0.171 | Destabilizing | 0.989 | D | 0.605 | neutral | N | 0.479398418 | None | None | I |
| K/P | 0.9477 | likely_pathogenic | 0.9534 | pathogenic | 0.12 | Stabilizing | 0.996 | D | 0.72 | prob.delet. | None | None | None | None | I |
| K/Q | 0.1278 | likely_benign | 0.1403 | benign | -0.256 | Destabilizing | 0.994 | D | 0.623 | neutral | N | 0.447998075 | None | None | I |
| K/R | 0.0807 | likely_benign | 0.0832 | benign | -0.391 | Destabilizing | 0.98 | D | 0.554 | neutral | N | 0.447171356 | None | None | I |
| K/S | 0.3971 | ambiguous | 0.4307 | ambiguous | -0.851 | Destabilizing | 0.559 | D | 0.285 | neutral | None | None | None | None | I |
| K/T | 0.1876 | likely_benign | 0.2122 | benign | -0.561 | Destabilizing | 0.925 | D | 0.66 | neutral | N | 0.429663031 | None | None | I |
| K/V | 0.3181 | likely_benign | 0.3697 | ambiguous | 0.12 | Stabilizing | 0.991 | D | 0.718 | prob.delet. | None | None | None | None | I |
| K/W | 0.8496 | likely_pathogenic | 0.8753 | pathogenic | -0.104 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| K/Y | 0.7214 | likely_pathogenic | 0.7624 | pathogenic | 0.178 | Stabilizing | 0.999 | D | 0.796 | 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.