Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29566 | 88921;88922;88923 | chr2:178554651;178554650;178554649 | chr2:179419378;179419377;179419376 |
| N2AB | 27925 | 83998;83999;84000 | chr2:178554651;178554650;178554649 | chr2:179419378;179419377;179419376 |
| N2A | 26998 | 81217;81218;81219 | chr2:178554651;178554650;178554649 | chr2:179419378;179419377;179419376 |
| N2B | 20501 | 61726;61727;61728 | chr2:178554651;178554650;178554649 | chr2:179419378;179419377;179419376 |
| Novex-1 | 20626 | 62101;62102;62103 | chr2:178554651;178554650;178554649 | chr2:179419378;179419377;179419376 |
| Novex-2 | 20693 | 62302;62303;62304 | chr2:178554651;178554650;178554649 | chr2:179419378;179419377;179419376 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs1700639038  |
None | 0.19 | N | 0.319 | 0.134 | 0.522397993787 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/L | rs1700639038 |
None | 0.19 | N | 0.319 | 0.134 | 0.522397993787 | gnomAD-4.0.0 | 3.09829E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22856E-05 | None | 0 | 0 | 3.39026E-06 | 0 | 0 |
| I/V | None | None | 0.001 | N | 0.138 | 0.103 | 0.418344901717 | gnomAD-4.0.0 | 6.84167E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99421E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9402 | likely_pathogenic | 0.9511 | pathogenic | -2.357 | Highly Destabilizing | 0.415 | N | 0.567 | neutral | None | None | None | None | N |
| I/C | 0.9467 | likely_pathogenic | 0.9633 | pathogenic | -1.336 | Destabilizing | 0.989 | D | 0.67 | neutral | None | None | None | None | N |
| I/D | 0.9949 | likely_pathogenic | 0.9962 | pathogenic | -2.402 | Highly Destabilizing | 0.987 | D | 0.787 | deleterious | None | None | None | None | N |
| I/E | 0.9871 | likely_pathogenic | 0.9882 | pathogenic | -2.328 | Highly Destabilizing | 0.961 | D | 0.776 | deleterious | None | None | None | None | N |
| I/F | 0.8773 | likely_pathogenic | 0.9183 | pathogenic | -1.645 | Destabilizing | 0.901 | D | 0.625 | neutral | D | 0.524865991 | None | None | N |
| I/G | 0.9879 | likely_pathogenic | 0.991 | pathogenic | -2.767 | Highly Destabilizing | 0.961 | D | 0.772 | deleterious | None | None | None | None | N |
| I/H | 0.9908 | likely_pathogenic | 0.9934 | pathogenic | -2.106 | Highly Destabilizing | 0.996 | D | 0.76 | deleterious | None | None | None | None | N |
| I/K | 0.9771 | likely_pathogenic | 0.9804 | pathogenic | -1.812 | Destabilizing | 0.961 | D | 0.777 | deleterious | None | None | None | None | N |
| I/L | 0.3623 | ambiguous | 0.4122 | ambiguous | -1.238 | Destabilizing | 0.19 | N | 0.319 | neutral | N | 0.479262959 | None | None | N |
| I/M | 0.4429 | ambiguous | 0.4965 | ambiguous | -0.811 | Destabilizing | 0.901 | D | 0.612 | neutral | D | 0.527400886 | None | None | N |
| I/N | 0.9139 | likely_pathogenic | 0.9246 | pathogenic | -1.738 | Destabilizing | 0.983 | D | 0.793 | deleterious | N | 0.521666895 | None | None | N |
| I/P | 0.9154 | likely_pathogenic | 0.9313 | pathogenic | -1.586 | Destabilizing | 0.987 | D | 0.785 | deleterious | None | None | None | None | N |
| I/Q | 0.9828 | likely_pathogenic | 0.9868 | pathogenic | -1.853 | Destabilizing | 0.987 | D | 0.791 | deleterious | None | None | None | None | N |
| I/R | 0.9725 | likely_pathogenic | 0.9781 | pathogenic | -1.192 | Destabilizing | 0.961 | D | 0.793 | deleterious | None | None | None | None | N |
| I/S | 0.9513 | likely_pathogenic | 0.9615 | pathogenic | -2.332 | Highly Destabilizing | 0.901 | D | 0.737 | prob.delet. | N | 0.51629807 | None | None | N |
| I/T | 0.8829 | likely_pathogenic | 0.9047 | pathogenic | -2.145 | Highly Destabilizing | 0.722 | D | 0.633 | neutral | N | 0.507081359 | None | None | N |
| I/V | 0.1018 | likely_benign | 0.1114 | benign | -1.586 | Destabilizing | 0.001 | N | 0.138 | neutral | N | 0.475117601 | None | None | N |
| I/W | 0.9957 | likely_pathogenic | 0.9977 | pathogenic | -1.898 | Destabilizing | 0.996 | D | 0.786 | deleterious | None | None | None | None | N |
| I/Y | 0.9729 | likely_pathogenic | 0.982 | pathogenic | -1.683 | Destabilizing | 0.961 | D | 0.699 | 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.