Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2429 | 7510;7511;7512 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
| N2AB | 2429 | 7510;7511;7512 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
| N2A | 2429 | 7510;7511;7512 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
| N2B | 2383 | 7372;7373;7374 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
| Novex-1 | 2383 | 7372;7373;7374 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
| Novex-2 | 2383 | 7372;7373;7374 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
| Novex-3 | 2429 | 7510;7511;7512 | chr2:178773883;178773882;178773881 | chr2:179638610;179638609;179638608 |
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 | None | None | 0.437 | N | 0.446 | 0.15 | 0.490352026379 | gnomAD-4.0.0 | 1.59059E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77377E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | None | None | 0.984 | N | 0.819 | 0.548 | 0.800198508981 | gnomAD-4.0.0 | 1.59059E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85665E-06 | 0 | 0 |
| I/T | rs148266341  |
None | 0.896 | N | 0.713 | 0.392 | None | gnomAD-4.0.0 | 1.59059E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85665E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8018 | likely_pathogenic | 0.7725 | pathogenic | -2.119 | Highly Destabilizing | 0.702 | D | 0.675 | neutral | None | None | None | None | N |
| I/C | 0.9058 | likely_pathogenic | 0.8813 | pathogenic | -1.566 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| I/D | 0.9724 | likely_pathogenic | 0.9684 | pathogenic | -1.757 | Destabilizing | 0.996 | D | 0.85 | deleterious | None | None | None | None | N |
| I/E | 0.965 | likely_pathogenic | 0.9603 | pathogenic | -1.529 | Destabilizing | 0.988 | D | 0.837 | deleterious | None | None | None | None | N |
| I/F | 0.4133 | ambiguous | 0.3715 | ambiguous | -1.167 | Destabilizing | 0.984 | D | 0.703 | prob.neutral | N | 0.498942996 | None | None | N |
| I/G | 0.9755 | likely_pathogenic | 0.9698 | pathogenic | -2.673 | Highly Destabilizing | 0.988 | D | 0.829 | deleterious | None | None | None | None | N |
| I/H | 0.9321 | likely_pathogenic | 0.9168 | pathogenic | -2.094 | Highly Destabilizing | 0.999 | D | 0.837 | deleterious | None | None | None | None | N |
| I/K | 0.9494 | likely_pathogenic | 0.9404 | pathogenic | -1.495 | Destabilizing | 0.988 | D | 0.837 | deleterious | None | None | None | None | N |
| I/L | 0.1525 | likely_benign | 0.1415 | benign | -0.539 | Destabilizing | 0.437 | N | 0.446 | neutral | N | 0.451978397 | None | None | N |
| I/M | 0.2121 | likely_benign | 0.1962 | benign | -0.624 | Destabilizing | 0.984 | D | 0.713 | prob.delet. | N | 0.498942996 | None | None | N |
| I/N | 0.7792 | likely_pathogenic | 0.7493 | pathogenic | -1.79 | Destabilizing | 0.995 | D | 0.857 | deleterious | N | 0.505191964 | None | None | N |
| I/P | 0.9791 | likely_pathogenic | 0.9769 | pathogenic | -1.043 | Destabilizing | 0.996 | D | 0.857 | deleterious | None | None | None | None | N |
| I/Q | 0.9351 | likely_pathogenic | 0.9233 | pathogenic | -1.599 | Destabilizing | 0.996 | D | 0.851 | deleterious | None | None | None | None | N |
| I/R | 0.9276 | likely_pathogenic | 0.9141 | pathogenic | -1.362 | Destabilizing | 0.996 | D | 0.856 | deleterious | None | None | None | None | N |
| I/S | 0.8093 | likely_pathogenic | 0.7804 | pathogenic | -2.597 | Highly Destabilizing | 0.984 | D | 0.819 | deleterious | N | 0.492888615 | None | None | N |
| I/T | 0.8478 | likely_pathogenic | 0.8217 | pathogenic | -2.205 | Highly Destabilizing | 0.896 | D | 0.713 | prob.delet. | N | 0.470399642 | None | None | N |
| I/V | 0.102 | likely_benign | 0.0955 | benign | -1.043 | Destabilizing | 0.004 | N | 0.291 | neutral | N | 0.365246964 | None | None | N |
| I/W | 0.9672 | likely_pathogenic | 0.9601 | pathogenic | -1.468 | Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | N |
| I/Y | 0.8641 | likely_pathogenic | 0.8384 | pathogenic | -1.148 | Destabilizing | 0.996 | D | 0.791 | deleterious | 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.