Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23176 | 69751;69752;69753 | chr2:178576718;178576717;178576716 | chr2:179441445;179441444;179441443 |
| N2AB | 21535 | 64828;64829;64830 | chr2:178576718;178576717;178576716 | chr2:179441445;179441444;179441443 |
| N2A | 20608 | 62047;62048;62049 | chr2:178576718;178576717;178576716 | chr2:179441445;179441444;179441443 |
| N2B | 14111 | 42556;42557;42558 | chr2:178576718;178576717;178576716 | chr2:179441445;179441444;179441443 |
| Novex-1 | 14236 | 42931;42932;42933 | chr2:178576718;178576717;178576716 | chr2:179441445;179441444;179441443 |
| Novex-2 | 14303 | 43132;43133;43134 | chr2:178576718;178576717;178576716 | chr2:179441445;179441444;179441443 |
| 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/A | rs1258714685  |
-2.696 | 0.334 | D | 0.625 | 0.45 | 0.677256655742 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| V/A | rs1258714685 |
-2.696 | 0.334 | D | 0.625 | 0.45 | 0.677256655742 | gnomAD-4.0.0 | 6.15864E-06 | None | None | None | None | N | None | 2.98918E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19663E-06 | 0 | 0 |
| V/E | rs1258714685 |
-3.231 | 0.781 | D | 0.856 | 0.67 | 0.846472525598 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/E | rs1258714685 |
-3.231 | 0.781 | D | 0.856 | 0.67 | 0.846472525598 | gnomAD-4.0.0 | 6.84293E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65684E-05 |
| V/I | rs1413591624 |
None | 0.002 | N | 0.256 | 0.057 | 0.159798565429 | 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 |
| V/I | rs1413591624 |
None | 0.002 | N | 0.256 | 0.057 | 0.159798565429 | gnomAD-4.0.0 | 3.84456E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.42777E-05 | None | 0 | 0 | 4.78776E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6815 | likely_pathogenic | 0.6841 | pathogenic | -2.487 | Highly Destabilizing | 0.334 | N | 0.625 | neutral | D | 0.527323024 | None | None | N |
| V/C | 0.9323 | likely_pathogenic | 0.9184 | pathogenic | -2.121 | Highly Destabilizing | 0.982 | D | 0.745 | deleterious | None | None | None | None | N |
| V/D | 0.9972 | likely_pathogenic | 0.9963 | pathogenic | -3.482 | Highly Destabilizing | 0.826 | D | 0.888 | deleterious | None | None | None | None | N |
| V/E | 0.988 | likely_pathogenic | 0.9854 | pathogenic | -3.202 | Highly Destabilizing | 0.781 | D | 0.856 | deleterious | D | 0.554581539 | None | None | N |
| V/F | 0.754 | likely_pathogenic | 0.6804 | pathogenic | -1.444 | Destabilizing | 0.7 | D | 0.757 | deleterious | None | None | None | None | N |
| V/G | 0.9063 | likely_pathogenic | 0.8971 | pathogenic | -3.073 | Highly Destabilizing | 0.781 | D | 0.877 | deleterious | D | 0.554581539 | None | None | N |
| V/H | 0.9961 | likely_pathogenic | 0.9945 | pathogenic | -2.89 | Highly Destabilizing | 0.982 | D | 0.855 | deleterious | None | None | None | None | N |
| V/I | 0.0782 | likely_benign | 0.0696 | benign | -0.802 | Destabilizing | 0.002 | N | 0.256 | neutral | N | 0.459380144 | None | None | N |
| V/K | 0.9884 | likely_pathogenic | 0.9846 | pathogenic | -2.254 | Highly Destabilizing | 0.826 | D | 0.857 | deleterious | None | None | None | None | N |
| V/L | 0.2414 | likely_benign | 0.2045 | benign | -0.802 | Destabilizing | 0.002 | N | 0.333 | neutral | N | 0.488860476 | None | None | N |
| V/M | 0.4118 | ambiguous | 0.3632 | ambiguous | -0.988 | Destabilizing | 0.7 | D | 0.651 | neutral | None | None | None | None | N |
| V/N | 0.9905 | likely_pathogenic | 0.9868 | pathogenic | -2.78 | Highly Destabilizing | 0.935 | D | 0.895 | deleterious | None | None | None | None | N |
| V/P | 0.968 | likely_pathogenic | 0.962 | pathogenic | -1.342 | Destabilizing | 0.935 | D | 0.878 | deleterious | None | None | None | None | N |
| V/Q | 0.9835 | likely_pathogenic | 0.9791 | pathogenic | -2.522 | Highly Destabilizing | 0.935 | D | 0.888 | deleterious | None | None | None | None | N |
| V/R | 0.9785 | likely_pathogenic | 0.9747 | pathogenic | -2.126 | Highly Destabilizing | 0.826 | D | 0.895 | deleterious | None | None | None | None | N |
| V/S | 0.9501 | likely_pathogenic | 0.9447 | pathogenic | -3.345 | Highly Destabilizing | 0.826 | D | 0.85 | deleterious | None | None | None | None | N |
| V/T | 0.7655 | likely_pathogenic | 0.7622 | pathogenic | -2.915 | Highly Destabilizing | 0.399 | N | 0.634 | neutral | None | None | None | None | N |
| V/W | 0.9918 | likely_pathogenic | 0.9882 | pathogenic | -2.049 | Highly Destabilizing | 0.982 | D | 0.834 | deleterious | None | None | None | None | N |
| V/Y | 0.9794 | likely_pathogenic | 0.9698 | pathogenic | -1.705 | Destabilizing | 0.826 | D | 0.765 | 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.