Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21023 | 63292;63293;63294 | chr2:178588658;178588657;178588656 | chr2:179453385;179453384;179453383 |
| N2AB | 19382 | 58369;58370;58371 | chr2:178588658;178588657;178588656 | chr2:179453385;179453384;179453383 |
| N2A | 18455 | 55588;55589;55590 | chr2:178588658;178588657;178588656 | chr2:179453385;179453384;179453383 |
| N2B | 11958 | 36097;36098;36099 | chr2:178588658;178588657;178588656 | chr2:179453385;179453384;179453383 |
| Novex-1 | 12083 | 36472;36473;36474 | chr2:178588658;178588657;178588656 | chr2:179453385;179453384;179453383 |
| Novex-2 | 12150 | 36673;36674;36675 | chr2:178588658;178588657;178588656 | chr2:179453385;179453384;179453383 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1060500596  |
None | 0.012 | N | 0.327 | 0.099 | 0.203808441222 | gnomAD-4.0.0 | 4.79745E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.76598E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/K | rs754385637 |
-0.782 | None | N | 0.209 | 0.286 | 0.510642626009 | gnomAD-2.1.1 | 2.43E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.99601E-04 | None | 0 | 0 | 0 |
| M/K | rs754385637 |
-0.782 | None | N | 0.209 | 0.286 | 0.510642626009 | gnomAD-4.0.0 | 8.22266E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00124E-07 | 1.16675E-04 | 1.6592E-05 |
| M/V | None | None | 0.005 | N | 0.261 | 0.163 | 0.0482279557977 | gnomAD-4.0.0 | 1.59669E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.44392E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4287 | ambiguous | 0.3928 | ambiguous | -2.102 | Highly Destabilizing | 0.014 | N | 0.349 | neutral | None | None | None | None | N |
| M/C | 0.4732 | ambiguous | 0.3952 | ambiguous | -1.894 | Destabilizing | None | N | 0.235 | neutral | None | None | None | None | N |
| M/D | 0.9302 | likely_pathogenic | 0.9069 | pathogenic | -1.222 | Destabilizing | 0.072 | N | 0.57 | neutral | None | None | None | None | N |
| M/E | 0.5953 | likely_pathogenic | 0.5154 | ambiguous | -1.045 | Destabilizing | 0.038 | N | 0.499 | neutral | None | None | None | None | N |
| M/F | 0.2249 | likely_benign | 0.2018 | benign | -0.656 | Destabilizing | 0.038 | N | 0.395 | neutral | None | None | None | None | N |
| M/G | 0.6537 | likely_pathogenic | 0.5951 | pathogenic | -2.555 | Highly Destabilizing | 0.072 | N | 0.47 | neutral | None | None | None | None | N |
| M/H | 0.4408 | ambiguous | 0.3588 | ambiguous | -1.82 | Destabilizing | 0.628 | D | 0.546 | neutral | None | None | None | None | N |
| M/I | 0.2806 | likely_benign | 0.276 | benign | -0.838 | Destabilizing | 0.012 | N | 0.327 | neutral | N | 0.426704791 | None | None | N |
| M/K | 0.1775 | likely_benign | 0.1429 | benign | -1.2 | Destabilizing | None | N | 0.209 | neutral | N | 0.492737782 | None | None | N |
| M/L | 0.0825 | likely_benign | 0.0849 | benign | -0.838 | Destabilizing | None | N | 0.087 | neutral | N | 0.401883704 | None | None | N |
| M/N | 0.6533 | likely_pathogenic | 0.591 | pathogenic | -1.424 | Destabilizing | 0.072 | N | 0.565 | neutral | None | None | None | None | N |
| M/P | 0.9788 | likely_pathogenic | 0.979 | pathogenic | -1.237 | Destabilizing | 0.136 | N | 0.594 | neutral | None | None | None | None | N |
| M/Q | 0.2036 | likely_benign | 0.1453 | benign | -1.214 | Destabilizing | 0.072 | N | 0.395 | neutral | None | None | None | None | N |
| M/R | 0.2148 | likely_benign | 0.174 | benign | -1.048 | Destabilizing | 0.029 | N | 0.46 | neutral | N | 0.468900023 | None | None | N |
| M/S | 0.5456 | ambiguous | 0.492 | ambiguous | -2.074 | Highly Destabilizing | 0.031 | N | 0.392 | neutral | None | None | None | None | N |
| M/T | 0.3843 | ambiguous | 0.3485 | ambiguous | -1.765 | Destabilizing | 0.024 | N | 0.396 | neutral | N | 0.442404962 | None | None | N |
| M/V | 0.11 | likely_benign | 0.1118 | benign | -1.237 | Destabilizing | 0.005 | N | 0.261 | neutral | N | 0.42477642 | None | None | N |
| M/W | 0.4877 | ambiguous | 0.449 | ambiguous | -0.817 | Destabilizing | 0.864 | D | 0.493 | neutral | None | None | None | None | N |
| M/Y | 0.3952 | ambiguous | 0.355 | ambiguous | -0.825 | Destabilizing | 0.356 | N | 0.525 | 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.