Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15391 | 46396;46397;46398 | chr2:178620350;178620349;178620348 | chr2:179485077;179485076;179485075 |
| N2AB | 13750 | 41473;41474;41475 | chr2:178620350;178620349;178620348 | chr2:179485077;179485076;179485075 |
| N2A | 12823 | 38692;38693;38694 | chr2:178620350;178620349;178620348 | chr2:179485077;179485076;179485075 |
| N2B | 6326 | 19201;19202;19203 | chr2:178620350;178620349;178620348 | chr2:179485077;179485076;179485075 |
| Novex-1 | 6451 | 19576;19577;19578 | chr2:178620350;178620349;178620348 | chr2:179485077;179485076;179485075 |
| Novex-2 | 6518 | 19777;19778;19779 | chr2:178620350;178620349;178620348 | chr2:179485077;179485076;179485075 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs775807236  |
-0.019 | 0.993 | D | 0.571 | 0.558 | 0.593515057505 | gnomAD-2.1.1 | 4.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.07E-06 | 0 |
| T/I | rs775807236 |
-0.019 | 0.993 | D | 0.571 | 0.558 | 0.593515057505 | gnomAD-4.0.0 | 6.19711E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 7.01016E-04 | 2.71169E-06 | 0 | 3.33778E-05 |
| T/R | None | None | 0.997 | D | 0.547 | 0.553 | 0.65667953858 | gnomAD-4.0.0 | 1.37714E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80779E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1003 | likely_benign | 0.1025 | benign | -0.556 | Destabilizing | 0.117 | N | 0.453 | neutral | D | 0.532236292 | None | None | N |
| T/C | 0.6228 | likely_pathogenic | 0.6888 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | N |
| T/D | 0.7344 | likely_pathogenic | 0.7938 | pathogenic | 0.151 | Stabilizing | 0.998 | D | 0.572 | neutral | None | None | None | None | N |
| T/E | 0.6541 | likely_pathogenic | 0.702 | pathogenic | 0.146 | Stabilizing | 0.995 | D | 0.543 | neutral | None | None | None | None | N |
| T/F | 0.6905 | likely_pathogenic | 0.7231 | pathogenic | -0.718 | Destabilizing | 0.998 | D | 0.603 | neutral | None | None | None | None | N |
| T/G | 0.4476 | ambiguous | 0.5065 | ambiguous | -0.79 | Destabilizing | 0.966 | D | 0.515 | neutral | None | None | None | None | N |
| T/H | 0.6988 | likely_pathogenic | 0.7544 | pathogenic | -0.995 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | N |
| T/I | 0.3746 | ambiguous | 0.3939 | ambiguous | -0.035 | Destabilizing | 0.993 | D | 0.571 | neutral | D | 0.548627519 | None | None | N |
| T/K | 0.6304 | likely_pathogenic | 0.6838 | pathogenic | -0.521 | Destabilizing | 0.993 | D | 0.541 | neutral | D | 0.547913703 | None | None | N |
| T/L | 0.2292 | likely_benign | 0.2096 | benign | -0.035 | Destabilizing | 0.983 | D | 0.568 | neutral | None | None | None | None | N |
| T/M | 0.2054 | likely_benign | 0.2044 | benign | -0.032 | Destabilizing | 1.0 | D | 0.588 | neutral | None | None | None | None | N |
| T/N | 0.3772 | ambiguous | 0.452 | ambiguous | -0.456 | Destabilizing | 0.998 | D | 0.605 | neutral | None | None | None | None | N |
| T/P | 0.2139 | likely_benign | 0.2058 | benign | -0.176 | Destabilizing | 0.997 | D | 0.563 | neutral | N | 0.498552089 | None | None | N |
| T/Q | 0.5919 | likely_pathogenic | 0.6411 | pathogenic | -0.556 | Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | None | N |
| T/R | 0.5701 | likely_pathogenic | 0.6122 | pathogenic | -0.329 | Destabilizing | 0.997 | D | 0.547 | neutral | D | 0.547913703 | None | None | N |
| T/S | 0.2324 | likely_benign | 0.2666 | benign | -0.727 | Destabilizing | 0.955 | D | 0.582 | neutral | D | 0.548292079 | None | None | N |
| T/V | 0.2135 | likely_benign | 0.2218 | benign | -0.176 | Destabilizing | 0.966 | D | 0.597 | neutral | None | None | None | None | N |
| T/W | 0.8984 | likely_pathogenic | 0.9035 | pathogenic | -0.703 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/Y | 0.71 | likely_pathogenic | 0.7308 | pathogenic | -0.432 | Destabilizing | 0.999 | D | 0.603 | 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.