Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32568 | 97927;97928;97929 | chr2:178541375;178541374;178541373 | chr2:179406102;179406101;179406100 |
| N2AB | 30927 | 93004;93005;93006 | chr2:178541375;178541374;178541373 | chr2:179406102;179406101;179406100 |
| N2A | 30000 | 90223;90224;90225 | chr2:178541375;178541374;178541373 | chr2:179406102;179406101;179406100 |
| N2B | 23503 | 70732;70733;70734 | chr2:178541375;178541374;178541373 | chr2:179406102;179406101;179406100 |
| Novex-1 | 23628 | 71107;71108;71109 | chr2:178541375;178541374;178541373 | chr2:179406102;179406101;179406100 |
| Novex-2 | 23695 | 71308;71309;71310 | chr2:178541375;178541374;178541373 | chr2:179406102;179406101;179406100 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/V | rs1694433744  |
None | 0.999 | N | 0.455 | 0.212 | 0.482574385019 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/V | rs1694433744 |
None | 0.999 | N | 0.455 | 0.212 | 0.482574385019 | gnomAD-4.0.0 | 6.21902E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4968E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.3487 | ambiguous | 0.3974 | ambiguous | -1.786 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| L/C | 0.4897 | ambiguous | 0.5302 | ambiguous | -0.926 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | N |
| L/D | 0.854 | likely_pathogenic | 0.887 | pathogenic | -1.369 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/E | 0.5582 | ambiguous | 0.6144 | pathogenic | -1.323 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| L/F | 0.2276 | likely_benign | 0.2843 | benign | -1.179 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.49373786 | None | None | N |
| L/G | 0.6494 | likely_pathogenic | 0.7112 | pathogenic | -2.153 | Highly Destabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | N |
| L/H | 0.3324 | likely_benign | 0.3936 | ambiguous | -1.38 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| L/I | 0.1366 | likely_benign | 0.1583 | benign | -0.826 | Destabilizing | 0.999 | D | 0.502 | neutral | N | 0.45433411 | None | None | N |
| L/K | 0.402 | ambiguous | 0.4747 | ambiguous | -1.224 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| L/M | 0.1247 | likely_benign | 0.1383 | benign | -0.572 | Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| L/N | 0.4021 | ambiguous | 0.4632 | ambiguous | -1.127 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| L/P | 0.9567 | likely_pathogenic | 0.9665 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| L/Q | 0.21 | likely_benign | 0.2508 | benign | -1.255 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| L/R | 0.2821 | likely_benign | 0.3622 | ambiguous | -0.653 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| L/S | 0.3948 | ambiguous | 0.4519 | ambiguous | -1.746 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.417679876 | None | None | N |
| L/T | 0.3144 | likely_benign | 0.3604 | ambiguous | -1.583 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/V | 0.138 | likely_benign | 0.1615 | benign | -1.116 | Destabilizing | 0.999 | D | 0.455 | neutral | N | 0.408311031 | None | None | N |
| L/W | 0.3699 | ambiguous | 0.4502 | ambiguous | -1.34 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| L/Y | 0.4659 | ambiguous | 0.527 | ambiguous | -1.087 | Destabilizing | 1.0 | D | 0.687 | prob.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.