Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26955 | 81088;81089;81090 | chr2:178565269;178565268;178565267 | chr2:179429996;179429995;179429994 |
| N2AB | 25314 | 76165;76166;76167 | chr2:178565269;178565268;178565267 | chr2:179429996;179429995;179429994 |
| N2A | 24387 | 73384;73385;73386 | chr2:178565269;178565268;178565267 | chr2:179429996;179429995;179429994 |
| N2B | 17890 | 53893;53894;53895 | chr2:178565269;178565268;178565267 | chr2:179429996;179429995;179429994 |
| Novex-1 | 18015 | 54268;54269;54270 | chr2:178565269;178565268;178565267 | chr2:179429996;179429995;179429994 |
| Novex-2 | 18082 | 54469;54470;54471 | chr2:178565269;178565268;178565267 | chr2:179429996;179429995;179429994 |
| 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/A | rs1336289056  |
-0.709 | 0.273 | N | 0.559 | 0.111 | 0.197625483188 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs1336289056 |
-0.709 | 0.273 | N | 0.559 | 0.111 | 0.197625483188 | gnomAD-4.0.0 | 1.59155E-06 | None | None | None | None | N | None | 0 | 2.28666E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs376947367 |
-0.11 | 0.864 | N | 0.722 | 0.566 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/I | rs376947367 |
-0.11 | 0.864 | N | 0.722 | 0.566 | None | gnomAD-4.0.0 | 1.59157E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85883E-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 | 0.0693 | likely_benign | 0.0679 | benign | -0.673 | Destabilizing | 0.273 | N | 0.559 | neutral | N | 0.497389532 | None | None | N |
| T/C | 0.2932 | likely_benign | 0.2847 | benign | -0.636 | Destabilizing | 0.985 | D | 0.718 | prob.delet. | None | None | None | None | N |
| T/D | 0.3859 | ambiguous | 0.3867 | ambiguous | -1.395 | Destabilizing | 0.894 | D | 0.666 | neutral | None | None | None | None | N |
| T/E | 0.2525 | likely_benign | 0.2492 | benign | -1.402 | Destabilizing | 0.809 | D | 0.672 | neutral | None | None | None | None | N |
| T/F | 0.2042 | likely_benign | 0.2091 | benign | -1.007 | Destabilizing | 0.945 | D | 0.769 | deleterious | None | None | None | None | N |
| T/G | 0.2021 | likely_benign | 0.1953 | benign | -0.892 | Destabilizing | 0.547 | D | 0.674 | neutral | None | None | None | None | N |
| T/H | 0.2084 | likely_benign | 0.1982 | benign | -1.31 | Destabilizing | 0.985 | D | 0.762 | deleterious | None | None | None | None | N |
| T/I | 0.12 | likely_benign | 0.1242 | benign | -0.183 | Destabilizing | 0.864 | D | 0.722 | prob.delet. | N | 0.500726527 | None | None | N |
| T/K | 0.1364 | likely_benign | 0.1266 | benign | -0.792 | Destabilizing | 0.761 | D | 0.671 | neutral | N | 0.493751795 | None | None | N |
| T/L | 0.1005 | likely_benign | 0.1075 | benign | -0.183 | Destabilizing | 0.707 | D | 0.652 | neutral | None | None | None | None | N |
| T/M | 0.0934 | likely_benign | 0.0941 | benign | 0.267 | Stabilizing | 0.995 | D | 0.714 | prob.delet. | None | None | None | None | N |
| T/N | 0.127 | likely_benign | 0.1245 | benign | -0.953 | Destabilizing | 0.809 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/P | 0.672 | likely_pathogenic | 0.6606 | pathogenic | -0.317 | Destabilizing | 0.928 | D | 0.721 | prob.delet. | D | 0.54302465 | None | None | N |
| T/Q | 0.1629 | likely_benign | 0.1535 | benign | -1.266 | Destabilizing | 0.894 | D | 0.718 | prob.delet. | None | None | None | None | N |
| T/R | 0.112 | likely_benign | 0.1102 | benign | -0.439 | Destabilizing | 0.864 | D | 0.721 | prob.delet. | N | 0.52090111 | None | None | N |
| T/S | 0.0878 | likely_benign | 0.0822 | benign | -1.018 | Destabilizing | 0.006 | N | 0.271 | neutral | N | 0.466162548 | None | None | N |
| T/V | 0.0908 | likely_benign | 0.0981 | benign | -0.317 | Destabilizing | 0.707 | D | 0.644 | neutral | None | None | None | None | N |
| T/W | 0.5267 | ambiguous | 0.5374 | ambiguous | -1.017 | Destabilizing | 0.995 | D | 0.774 | deleterious | None | None | None | None | N |
| T/Y | 0.2489 | likely_benign | 0.2451 | benign | -0.698 | Destabilizing | 0.945 | D | 0.77 | 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.