Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14544 | 43855;43856;43857 | chr2:178632264;178632263;178632262 | chr2:179496991;179496990;179496989 |
| N2AB | 12903 | 38932;38933;38934 | chr2:178632264;178632263;178632262 | chr2:179496991;179496990;179496989 |
| N2A | 11976 | 36151;36152;36153 | chr2:178632264;178632263;178632262 | chr2:179496991;179496990;179496989 |
| N2B | 5479 | 16660;16661;16662 | chr2:178632264;178632263;178632262 | chr2:179496991;179496990;179496989 |
| Novex-1 | 5604 | 17035;17036;17037 | chr2:178632264;178632263;178632262 | chr2:179496991;179496990;179496989 |
| Novex-2 | 5671 | 17236;17237;17238 | chr2:178632264;178632263;178632262 | chr2:179496991;179496990;179496989 |
| 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 | rs774916528  |
-0.371 | 0.238 | N | 0.129 | 0.306 | 0.468834750356 | gnomAD-2.1.1 | 1.24E-05 | None | None | None | None | N | None | 1.36203E-04 | 0 | None | 0 | 5.76E-05 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs774916528 |
-0.371 | 0.238 | N | 0.129 | 0.306 | 0.468834750356 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20709E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs774916528 |
-0.371 | 0.238 | N | 0.129 | 0.306 | 0.468834750356 | gnomAD-4.0.0 | 1.03081E-05 | None | None | None | None | N | None | 1.18576E-04 | 0 | None | 0 | 2.44618E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs1576685386 |
None | 0.979 | N | 0.453 | 0.477 | 0.770758717093 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/V | rs1046991494 |
-0.645 | 0.677 | N | 0.243 | 0.299 | 0.519351293798 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.37E-05 | None | 0 | 0 | 0 |
| M/V | rs1046991494 |
-0.645 | 0.677 | N | 0.243 | 0.299 | 0.519351293798 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs1046991494 |
-0.645 | 0.677 | N | 0.243 | 0.299 | 0.519351293798 | gnomAD-4.0.0 | 3.10662E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39609E-06 | 1.10757E-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 | 0.7336 | likely_pathogenic | 0.6668 | pathogenic | -1.722 | Destabilizing | 0.963 | D | 0.369 | neutral | None | None | None | None | N |
| M/C | 0.8726 | likely_pathogenic | 0.8734 | pathogenic | -1.312 | Destabilizing | 1.0 | D | 0.511 | neutral | None | None | None | None | N |
| M/D | 0.9612 | likely_pathogenic | 0.9585 | pathogenic | -0.289 | Destabilizing | 0.999 | D | 0.58 | neutral | None | None | None | None | N |
| M/E | 0.724 | likely_pathogenic | 0.7002 | pathogenic | -0.216 | Destabilizing | 0.999 | D | 0.554 | neutral | None | None | None | None | N |
| M/F | 0.4283 | ambiguous | 0.3993 | ambiguous | -0.704 | Destabilizing | 0.969 | D | 0.466 | neutral | None | None | None | None | N |
| M/G | 0.8815 | likely_pathogenic | 0.852 | pathogenic | -2.079 | Highly Destabilizing | 0.995 | D | 0.557 | neutral | None | None | None | None | N |
| M/H | 0.7755 | likely_pathogenic | 0.7538 | pathogenic | -1.229 | Destabilizing | 1.0 | D | 0.545 | neutral | None | None | None | None | N |
| M/I | 0.5245 | ambiguous | 0.4379 | ambiguous | -0.778 | Destabilizing | 0.238 | N | 0.129 | neutral | N | 0.450589958 | None | None | N |
| M/K | 0.4054 | ambiguous | 0.3364 | benign | -0.34 | Destabilizing | 0.993 | D | 0.509 | neutral | D | 0.604076614 | None | None | N |
| M/L | 0.2073 | likely_benign | 0.1794 | benign | -0.778 | Destabilizing | 0.03 | N | 0.101 | neutral | N | 0.507302617 | None | None | N |
| M/N | 0.8568 | likely_pathogenic | 0.8424 | pathogenic | -0.316 | Destabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | N |
| M/P | 0.9538 | likely_pathogenic | 0.9473 | pathogenic | -1.066 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | N |
| M/Q | 0.4247 | ambiguous | 0.3984 | ambiguous | -0.296 | Destabilizing | 0.999 | D | 0.497 | neutral | None | None | None | None | N |
| M/R | 0.3686 | ambiguous | 0.336 | benign | -0.08 | Destabilizing | 0.998 | D | 0.555 | neutral | D | 0.604743897 | None | None | N |
| M/S | 0.7244 | likely_pathogenic | 0.6921 | pathogenic | -0.994 | Destabilizing | 0.995 | D | 0.467 | neutral | None | None | None | None | N |
| M/T | 0.4825 | ambiguous | 0.4306 | ambiguous | -0.789 | Destabilizing | 0.979 | D | 0.453 | neutral | N | 0.499531806 | None | None | N |
| M/V | 0.1413 | likely_benign | 0.1269 | benign | -1.066 | Destabilizing | 0.677 | D | 0.243 | neutral | N | 0.495955602 | None | None | N |
| M/W | 0.7503 | likely_pathogenic | 0.7495 | pathogenic | -0.671 | Destabilizing | 1.0 | D | 0.521 | neutral | None | None | None | None | N |
| M/Y | 0.7709 | likely_pathogenic | 0.7436 | pathogenic | -0.655 | Destabilizing | 0.999 | D | 0.545 | 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.