Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17067 | 51424;51425;51426 | chr2:178610327;178610326;178610325 | chr2:179475054;179475053;179475052 |
| N2AB | 15426 | 46501;46502;46503 | chr2:178610327;178610326;178610325 | chr2:179475054;179475053;179475052 |
| N2A | 14499 | 43720;43721;43722 | chr2:178610327;178610326;178610325 | chr2:179475054;179475053;179475052 |
| N2B | 8002 | 24229;24230;24231 | chr2:178610327;178610326;178610325 | chr2:179475054;179475053;179475052 |
| Novex-1 | 8127 | 24604;24605;24606 | chr2:178610327;178610326;178610325 | chr2:179475054;179475053;179475052 |
| Novex-2 | 8194 | 24805;24806;24807 | chr2:178610327;178610326;178610325 | chr2:179475054;179475053;179475052 |
| 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 | rs1045892065  |
-1.08 | 0.64 | N | 0.466 | 0.122 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/A | rs1045892065 |
-1.08 | 0.64 | N | 0.466 | 0.122 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/A | rs1045892065 |
-1.08 | 0.64 | N | 0.466 | 0.122 | None | gnomAD-4.0.0 | 1.15436E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.15662E-05 | 0 | 0 |
| T/I | None | None | 0.984 | N | 0.607 | 0.418 | 0.480497669815 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.1047 | likely_benign | 0.0971 | benign | -1.009 | Destabilizing | 0.64 | D | 0.466 | neutral | N | 0.465951181 | None | None | N |
| T/C | 0.3543 | ambiguous | 0.3591 | ambiguous | -0.644 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| T/D | 0.5541 | ambiguous | 0.4716 | ambiguous | -0.786 | Destabilizing | 0.919 | D | 0.518 | neutral | None | None | None | None | N |
| T/E | 0.4616 | ambiguous | 0.3847 | ambiguous | -0.657 | Destabilizing | 0.919 | D | 0.511 | neutral | None | None | None | None | N |
| T/F | 0.2254 | likely_benign | 0.2013 | benign | -0.717 | Destabilizing | 0.996 | D | 0.716 | prob.delet. | None | None | None | None | N |
| T/G | 0.2471 | likely_benign | 0.2358 | benign | -1.384 | Destabilizing | 0.851 | D | 0.57 | neutral | None | None | None | None | N |
| T/H | 0.2857 | likely_benign | 0.2545 | benign | -1.553 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/I | 0.1706 | likely_benign | 0.157 | benign | -0.055 | Destabilizing | 0.984 | D | 0.607 | neutral | N | 0.486306123 | None | None | N |
| T/K | 0.4652 | ambiguous | 0.3907 | ambiguous | -0.598 | Destabilizing | 0.919 | D | 0.515 | neutral | None | None | None | None | N |
| T/L | 0.1145 | likely_benign | 0.1044 | benign | -0.055 | Destabilizing | 0.919 | D | 0.492 | neutral | None | None | None | None | N |
| T/M | 0.0997 | likely_benign | 0.0958 | benign | -0.002 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/N | 0.1445 | likely_benign | 0.1313 | benign | -0.955 | Destabilizing | 0.896 | D | 0.441 | neutral | N | 0.481498597 | None | None | N |
| T/P | 0.8964 | likely_pathogenic | 0.8418 | pathogenic | -0.34 | Destabilizing | 0.984 | D | 0.606 | neutral | D | 0.618973035 | None | None | N |
| T/Q | 0.279 | likely_benign | 0.2421 | benign | -0.875 | Destabilizing | 0.988 | D | 0.665 | neutral | None | None | None | None | N |
| T/R | 0.4444 | ambiguous | 0.3587 | ambiguous | -0.651 | Destabilizing | 0.976 | D | 0.652 | neutral | None | None | None | None | N |
| T/S | 0.0889 | likely_benign | 0.0864 | benign | -1.231 | Destabilizing | 0.046 | N | 0.268 | neutral | N | 0.396739104 | None | None | N |
| T/V | 0.1352 | likely_benign | 0.1296 | benign | -0.34 | Destabilizing | 0.919 | D | 0.401 | neutral | None | None | None | None | N |
| T/W | 0.6535 | likely_pathogenic | 0.6004 | pathogenic | -0.768 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3061 | likely_benign | 0.2816 | benign | -0.451 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | 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.