Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17647 | 53164;53165;53166 | chr2:178607848;178607847;178607846 | chr2:179472575;179472574;179472573 |
| N2AB | 16006 | 48241;48242;48243 | chr2:178607848;178607847;178607846 | chr2:179472575;179472574;179472573 |
| N2A | 15079 | 45460;45461;45462 | chr2:178607848;178607847;178607846 | chr2:179472575;179472574;179472573 |
| N2B | 8582 | 25969;25970;25971 | chr2:178607848;178607847;178607846 | chr2:179472575;179472574;179472573 |
| Novex-1 | 8707 | 26344;26345;26346 | chr2:178607848;178607847;178607846 | chr2:179472575;179472574;179472573 |
| Novex-2 | 8774 | 26545;26546;26547 | chr2:178607848;178607847;178607846 | chr2:179472575;179472574;179472573 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | None | None | 0.963 | N | 0.641 | 0.45 | 0.847466415278 | gnomAD-4.0.0 | 1.59277E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86105E-06 | 0 | 0 |
| V/I | rs2055289563  |
None | 0.002 | N | 0.173 | 0.057 | 0.448891444097 | gnomAD-4.0.0 | 3.42244E-06 | None | None | None | None | N | None | 2.99204E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69925E-06 | 0 | 1.65772E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3589 | ambiguous | 0.2769 | benign | -1.765 | Destabilizing | 0.334 | N | 0.459 | neutral | D | 0.530338952 | None | None | N |
| V/C | 0.7265 | likely_pathogenic | 0.6429 | pathogenic | -1.45 | Destabilizing | 0.005 | N | 0.355 | neutral | None | None | None | None | N |
| V/D | 0.8488 | likely_pathogenic | 0.8045 | pathogenic | -1.696 | Destabilizing | 0.963 | D | 0.641 | neutral | N | 0.506778644 | None | None | N |
| V/E | 0.6156 | likely_pathogenic | 0.528 | ambiguous | -1.603 | Destabilizing | 0.972 | D | 0.59 | neutral | None | None | None | None | N |
| V/F | 0.2515 | likely_benign | 0.197 | benign | -1.181 | Destabilizing | 0.81 | D | 0.607 | neutral | N | 0.490369456 | None | None | N |
| V/G | 0.5194 | ambiguous | 0.444 | ambiguous | -2.178 | Highly Destabilizing | 0.896 | D | 0.636 | neutral | N | 0.495168849 | None | None | N |
| V/H | 0.789 | likely_pathogenic | 0.6981 | pathogenic | -1.698 | Destabilizing | 0.992 | D | 0.635 | neutral | None | None | None | None | N |
| V/I | 0.0895 | likely_benign | 0.0789 | benign | -0.683 | Destabilizing | 0.002 | N | 0.173 | neutral | N | 0.469386494 | None | None | N |
| V/K | 0.4937 | ambiguous | 0.4152 | ambiguous | -1.334 | Destabilizing | 0.92 | D | 0.599 | neutral | None | None | None | None | N |
| V/L | 0.2565 | likely_benign | 0.2065 | benign | -0.683 | Destabilizing | 0.002 | N | 0.189 | neutral | N | 0.520063243 | None | None | N |
| V/M | 0.1915 | likely_benign | 0.1398 | benign | -0.738 | Destabilizing | 0.85 | D | 0.567 | neutral | None | None | None | None | N |
| V/N | 0.6953 | likely_pathogenic | 0.6122 | pathogenic | -1.332 | Destabilizing | 0.972 | D | 0.651 | neutral | None | None | None | None | N |
| V/P | 0.9843 | likely_pathogenic | 0.9829 | pathogenic | -1.011 | Destabilizing | 0.972 | D | 0.578 | neutral | None | None | None | None | N |
| V/Q | 0.4942 | ambiguous | 0.4061 | ambiguous | -1.387 | Destabilizing | 0.972 | D | 0.574 | neutral | None | None | None | None | N |
| V/R | 0.4366 | ambiguous | 0.3688 | ambiguous | -0.975 | Destabilizing | 0.92 | D | 0.655 | neutral | None | None | None | None | N |
| V/S | 0.4966 | ambiguous | 0.4032 | ambiguous | -1.984 | Destabilizing | 0.766 | D | 0.585 | neutral | None | None | None | None | N |
| V/T | 0.3628 | ambiguous | 0.2875 | benign | -1.765 | Destabilizing | 0.617 | D | 0.538 | neutral | None | None | None | None | N |
| V/W | 0.8868 | likely_pathogenic | 0.8204 | pathogenic | -1.45 | Destabilizing | 0.992 | D | 0.661 | neutral | None | None | None | None | N |
| V/Y | 0.6937 | likely_pathogenic | 0.6086 | pathogenic | -1.118 | Destabilizing | 0.92 | D | 0.597 | 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.