Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27761 | 83506;83507;83508 | chr2:178562851;178562850;178562849 | chr2:179427578;179427577;179427576 |
| N2AB | 26120 | 78583;78584;78585 | chr2:178562851;178562850;178562849 | chr2:179427578;179427577;179427576 |
| N2A | 25193 | 75802;75803;75804 | chr2:178562851;178562850;178562849 | chr2:179427578;179427577;179427576 |
| N2B | 18696 | 56311;56312;56313 | chr2:178562851;178562850;178562849 | chr2:179427578;179427577;179427576 |
| Novex-1 | 18821 | 56686;56687;56688 | chr2:178562851;178562850;178562849 | chr2:179427578;179427577;179427576 |
| Novex-2 | 18888 | 56887;56888;56889 | chr2:178562851;178562850;178562849 | chr2:179427578;179427577;179427576 |
| 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 | rs371788070  |
-0.383 | 0.999 | N | 0.539 | 0.288 | None | gnomAD-2.1.1 | 1.62027E-04 | None | None | None | None | N | None | 1.2499E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.23533E-04 | 1.41603E-04 |
| V/I | rs371788070 |
-0.383 | 0.999 | N | 0.539 | 0.288 | None | gnomAD-3.1.2 | 1.90692E-04 | None | None | None | None | N | None | 2.41429E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.79338E-04 | 0 | 0 |
| V/I | rs371788070 |
-0.383 | 0.999 | N | 0.539 | 0.288 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| V/I | rs371788070 |
-0.383 | 0.999 | N | 0.539 | 0.288 | None | gnomAD-4.0.0 | 3.53407E-04 | None | None | None | None | N | None | 2.66667E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 4.54453E-04 | 0 | 2.2433E-04 |
| V/L | rs371788070 |
-0.385 | 0.999 | N | 0.643 | 0.337 | None | gnomAD-2.1.1 | 8.28E-05 | None | None | None | None | N | None | 4.17E-05 | 5.7E-05 | None | 1.9478E-04 | 0 | None | 0 | None | 0 | 1.42039E-04 | 0 |
| V/L | rs371788070 |
-0.385 | 0.999 | N | 0.643 | 0.337 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17616E-04 | 0 | 0 |
| V/L | rs371788070 |
-0.385 | 0.999 | N | 0.643 | 0.337 | None | gnomAD-4.0.0 | 1.32692E-04 | None | None | None | None | N | None | 2.67101E-05 | 3.34113E-05 | None | 6.7627E-05 | 0 | None | 0 | 0 | 1.72962E-04 | 0 | 6.41169E-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 | 0.9456 | likely_pathogenic | 0.9483 | pathogenic | -2.176 | Highly Destabilizing | 0.999 | D | 0.622 | neutral | D | 0.533485321 | None | None | N |
| V/C | 0.9706 | likely_pathogenic | 0.9702 | pathogenic | -1.882 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| V/D | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -2.68 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.5339923 | None | None | N |
| V/E | 0.9985 | likely_pathogenic | 0.9985 | pathogenic | -2.434 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| V/F | 0.9627 | likely_pathogenic | 0.9569 | pathogenic | -1.29 | Destabilizing | 1.0 | D | 0.831 | deleterious | N | 0.521368547 | None | None | N |
| V/G | 0.9732 | likely_pathogenic | 0.9757 | pathogenic | -2.758 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | D | 0.5339923 | None | None | N |
| V/H | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.534 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/I | 0.1764 | likely_benign | 0.1526 | benign | -0.54 | Destabilizing | 0.999 | D | 0.539 | neutral | N | 0.480788263 | None | None | N |
| V/K | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| V/L | 0.8596 | likely_pathogenic | 0.8254 | pathogenic | -0.54 | Destabilizing | 0.999 | D | 0.643 | neutral | N | 0.443464348 | None | None | N |
| V/M | 0.9151 | likely_pathogenic | 0.9068 | pathogenic | -0.687 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| V/N | 0.9979 | likely_pathogenic | 0.9979 | pathogenic | -2.249 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| V/P | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -1.058 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| V/Q | 0.9982 | likely_pathogenic | 0.9983 | pathogenic | -2.032 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/R | 0.9969 | likely_pathogenic | 0.9971 | pathogenic | -1.764 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| V/S | 0.9904 | likely_pathogenic | 0.9909 | pathogenic | -2.925 | Highly Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| V/T | 0.949 | likely_pathogenic | 0.9521 | pathogenic | -2.517 | Highly Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| V/W | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -1.811 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Y | 0.9975 | likely_pathogenic | 0.9974 | pathogenic | -1.429 | Destabilizing | 1.0 | D | 0.827 | 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.