Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27609 | 83050;83051;83052 | chr2:178563307;178563306;178563305 | chr2:179428034;179428033;179428032 |
| N2AB | 25968 | 78127;78128;78129 | chr2:178563307;178563306;178563305 | chr2:179428034;179428033;179428032 |
| N2A | 25041 | 75346;75347;75348 | chr2:178563307;178563306;178563305 | chr2:179428034;179428033;179428032 |
| N2B | 18544 | 55855;55856;55857 | chr2:178563307;178563306;178563305 | chr2:179428034;179428033;179428032 |
| Novex-1 | 18669 | 56230;56231;56232 | chr2:178563307;178563306;178563305 | chr2:179428034;179428033;179428032 |
| Novex-2 | 18736 | 56431;56432;56433 | chr2:178563307;178563306;178563305 | chr2:179428034;179428033;179428032 |
| 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/I | rs767367789  |
-0.173 | 0.012 | N | 0.325 | 0.082 | 0.301455362545 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11869E-04 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs767367789 |
-0.173 | 0.012 | N | 0.325 | 0.082 | 0.301455362545 | gnomAD-4.0.0 | 3.18322E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.55648E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs767367789 |
None | None | N | 0.163 | 0.084 | 0.357313475932 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/L | rs767367789 |
None | None | N | 0.163 | 0.084 | 0.357313475932 | gnomAD-4.0.0 | 5.12552E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57382E-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 | 0.1618 | likely_benign | 0.1792 | benign | -1.605 | Destabilizing | None | N | 0.145 | neutral | N | 0.378241628 | None | None | N |
| V/C | 0.4871 | ambiguous | 0.5464 | ambiguous | -0.784 | Destabilizing | None | N | 0.541 | neutral | None | None | None | None | N |
| V/D | 0.7305 | likely_pathogenic | 0.722 | pathogenic | -2.539 | Highly Destabilizing | 0.106 | N | 0.765 | deleterious | N | 0.516289432 | None | None | N |
| V/E | 0.441 | ambiguous | 0.4261 | ambiguous | -2.215 | Highly Destabilizing | 0.072 | N | 0.729 | prob.delet. | None | None | None | None | N |
| V/F | 0.1105 | likely_benign | 0.1425 | benign | -0.868 | Destabilizing | None | N | 0.437 | neutral | N | 0.435711063 | None | None | N |
| V/G | 0.2604 | likely_benign | 0.2562 | benign | -2.207 | Highly Destabilizing | 0.012 | N | 0.685 | prob.neutral | N | 0.478944553 | None | None | N |
| V/H | 0.5645 | likely_pathogenic | 0.6053 | pathogenic | -2.388 | Highly Destabilizing | 0.628 | D | 0.767 | deleterious | None | None | None | None | N |
| V/I | 0.0771 | likely_benign | 0.0835 | benign | 0.144 | Stabilizing | 0.012 | N | 0.325 | neutral | N | 0.404734796 | None | None | N |
| V/K | 0.316 | likely_benign | 0.289 | benign | -0.944 | Destabilizing | 0.016 | N | 0.669 | neutral | None | None | None | None | N |
| V/L | 0.1467 | likely_benign | 0.1482 | benign | 0.144 | Stabilizing | None | N | 0.163 | neutral | N | 0.439884732 | None | None | N |
| V/M | 0.0729 | likely_benign | 0.0831 | benign | -0.135 | Destabilizing | 0.003 | N | 0.218 | neutral | None | None | None | None | N |
| V/N | 0.514 | ambiguous | 0.5276 | ambiguous | -1.647 | Destabilizing | 0.136 | N | 0.782 | deleterious | None | None | None | None | N |
| V/P | 0.9822 | likely_pathogenic | 0.9817 | pathogenic | -0.42 | Destabilizing | 0.136 | N | 0.775 | deleterious | None | None | None | None | N |
| V/Q | 0.2916 | likely_benign | 0.3056 | benign | -1.234 | Destabilizing | 0.072 | N | 0.768 | deleterious | None | None | None | None | N |
| V/R | 0.2963 | likely_benign | 0.2939 | benign | -1.362 | Destabilizing | None | N | 0.608 | neutral | None | None | None | None | N |
| V/S | 0.2383 | likely_benign | 0.2767 | benign | -2.08 | Highly Destabilizing | 0.016 | N | 0.663 | neutral | None | None | None | None | N |
| V/T | 0.2213 | likely_benign | 0.2325 | benign | -1.592 | Destabilizing | 0.031 | N | 0.469 | neutral | None | None | None | None | N |
| V/W | 0.6235 | likely_pathogenic | 0.676 | pathogenic | -1.465 | Destabilizing | 0.864 | D | 0.762 | deleterious | None | None | None | None | N |
| V/Y | 0.3403 | ambiguous | 0.3988 | ambiguous | -1.043 | Destabilizing | 0.038 | N | 0.749 | 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.