Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20426 | 61501;61502;61503 | chr2:178590449;178590448;178590447 | chr2:179455176;179455175;179455174 |
| N2AB | 18785 | 56578;56579;56580 | chr2:178590449;178590448;178590447 | chr2:179455176;179455175;179455174 |
| N2A | 17858 | 53797;53798;53799 | chr2:178590449;178590448;178590447 | chr2:179455176;179455175;179455174 |
| N2B | 11361 | 34306;34307;34308 | chr2:178590449;178590448;178590447 | chr2:179455176;179455175;179455174 |
| Novex-1 | 11486 | 34681;34682;34683 | chr2:178590449;178590448;178590447 | chr2:179455176;179455175;179455174 |
| Novex-2 | 11553 | 34882;34883;34884 | chr2:178590449;178590448;178590447 | chr2:179455176;179455175;179455174 |
| 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 | rs377529060  |
-1.431 | 0.217 | N | 0.319 | 0.186 | 0.361360026772 | gnomAD-2.1.1 | 8.59E-05 | None | None | None | None | N | None | 0 | 2.84E-05 | None | 0 | 1.03146E-03 | None | 0 | None | 0 | 0 | 4.23012E-04 |
| L/F | rs377529060 |
-1.431 | 0.217 | N | 0.319 | 0.186 | 0.361360026772 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 9.71251E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs377529060 |
-1.431 | 0.217 | N | 0.319 | 0.186 | 0.361360026772 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| L/F | rs377529060 |
-1.431 | 0.217 | N | 0.319 | 0.186 | 0.361360026772 | gnomAD-4.0.0 | 2.72788E-05 | None | None | None | None | N | None | 0 | 3.33745E-05 | None | 0 | 5.36481E-04 | None | 0 | 0 | 1.69578E-06 | 0 | 2.56205E-04 |
| L/H | None | None | 1.0 | N | 0.77 | 0.402 | 0.827319285163 | gnomAD-4.0.0 | 1.59304E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86107E-06 | 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 | 0.6425 | likely_pathogenic | 0.6062 | pathogenic | -1.542 | Destabilizing | 0.996 | D | 0.552 | neutral | None | None | None | None | N |
| L/C | 0.7826 | likely_pathogenic | 0.7863 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/D | 0.9253 | likely_pathogenic | 0.9151 | pathogenic | -0.892 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| L/E | 0.7801 | likely_pathogenic | 0.7422 | pathogenic | -0.904 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/F | 0.3717 | ambiguous | 0.3168 | benign | -1.071 | Destabilizing | 0.217 | N | 0.319 | neutral | N | 0.471595821 | None | None | N |
| L/G | 0.8287 | likely_pathogenic | 0.8023 | pathogenic | -1.844 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| L/H | 0.6702 | likely_pathogenic | 0.6462 | pathogenic | -1.026 | Destabilizing | 1.0 | D | 0.77 | deleterious | N | 0.497103452 | None | None | N |
| L/I | 0.2303 | likely_benign | 0.2064 | benign | -0.797 | Destabilizing | 0.989 | D | 0.395 | neutral | N | 0.502645345 | None | None | N |
| L/K | 0.6106 | likely_pathogenic | 0.5845 | pathogenic | -0.945 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| L/M | 0.2011 | likely_benign | 0.1946 | benign | -0.631 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| L/N | 0.7059 | likely_pathogenic | 0.6733 | pathogenic | -0.725 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/P | 0.457 | ambiguous | 0.4041 | ambiguous | -1.014 | Destabilizing | 0.999 | D | 0.793 | deleterious | N | 0.455024756 | None | None | N |
| L/Q | 0.5312 | ambiguous | 0.5162 | ambiguous | -0.938 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| L/R | 0.5826 | likely_pathogenic | 0.563 | ambiguous | -0.353 | Destabilizing | 0.999 | D | 0.771 | deleterious | N | 0.503472064 | None | None | N |
| L/S | 0.8277 | likely_pathogenic | 0.7875 | pathogenic | -1.347 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| L/T | 0.6228 | likely_pathogenic | 0.5637 | ambiguous | -1.248 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| L/V | 0.2422 | likely_benign | 0.2235 | benign | -1.014 | Destabilizing | 0.989 | D | 0.418 | neutral | N | 0.489580047 | None | None | N |
| L/W | 0.5357 | ambiguous | 0.512 | ambiguous | -1.096 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | N |
| L/Y | 0.6186 | likely_pathogenic | 0.5607 | ambiguous | -0.884 | Destabilizing | 0.995 | D | 0.703 | 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.