Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17184 | 51775;51776;51777 | chr2:178609873;178609872;178609871 | chr2:179474600;179474599;179474598 |
| N2AB | 15543 | 46852;46853;46854 | chr2:178609873;178609872;178609871 | chr2:179474600;179474599;179474598 |
| N2A | 14616 | 44071;44072;44073 | chr2:178609873;178609872;178609871 | chr2:179474600;179474599;179474598 |
| N2B | 8119 | 24580;24581;24582 | chr2:178609873;178609872;178609871 | chr2:179474600;179474599;179474598 |
| Novex-1 | 8244 | 24955;24956;24957 | chr2:178609873;178609872;178609871 | chr2:179474600;179474599;179474598 |
| Novex-2 | 8311 | 25156;25157;25158 | chr2:178609873;178609872;178609871 | chr2:179474600;179474599;179474598 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs767319592  |
-1.645 | 0.934 | N | 0.623 | 0.382 | 0.525613252392 | gnomAD-2.1.1 | 3.62E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.94175E-04 | None | 0 | 0 | 0 |
| I/M | rs767319592 |
-1.645 | 0.934 | N | 0.623 | 0.382 | 0.525613252392 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-04 | 0 |
| I/M | rs767319592 |
-1.645 | 0.934 | N | 0.623 | 0.382 | 0.525613252392 | gnomAD-4.0.0 | 8.05965E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47968E-07 | 1.20799E-04 | 1.60241E-05 |
| I/T | rs752646731 |
-3.469 | 0.891 | D | 0.663 | 0.489 | 0.773765334734 | gnomAD-2.1.1 | 5.23E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 2.94175E-04 | None | 0 | 2.67E-05 | 0 |
| I/T | rs752646731 |
-3.469 | 0.891 | D | 0.663 | 0.489 | 0.773765334734 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs752646731 |
-3.469 | 0.891 | D | 0.663 | 0.489 | 0.773765334734 | gnomAD-4.0.0 | 5.51798E-05 | None | None | None | None | N | None | 1.33626E-05 | 0 | None | 0 | 4.46349E-05 | None | 0 | 0 | 5.4271E-05 | 2.19664E-04 | 3.20482E-05 |
| I/V | rs777442915 |
-1.901 | 0.267 | N | 0.291 | 0.1 | 0.313210971179 | gnomAD-4.0.0 | 4.77791E-06 | None | None | None | None | N | None | 5.67022E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72315E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9319 | likely_pathogenic | 0.9206 | pathogenic | -3.232 | Highly Destabilizing | 0.688 | D | 0.666 | neutral | None | None | None | None | N |
| I/C | 0.9778 | likely_pathogenic | 0.9745 | pathogenic | -2.343 | Highly Destabilizing | 0.998 | D | 0.783 | deleterious | None | None | None | None | N |
| I/D | 0.9997 | likely_pathogenic | 0.9995 | pathogenic | -3.799 | Highly Destabilizing | 0.991 | D | 0.863 | deleterious | None | None | None | None | N |
| I/E | 0.9984 | likely_pathogenic | 0.9978 | pathogenic | -3.508 | Highly Destabilizing | 0.991 | D | 0.849 | deleterious | None | None | None | None | N |
| I/F | 0.9208 | likely_pathogenic | 0.911 | pathogenic | -1.962 | Destabilizing | 0.949 | D | 0.661 | neutral | None | None | None | None | N |
| I/G | 0.997 | likely_pathogenic | 0.9961 | pathogenic | -3.761 | Highly Destabilizing | 0.991 | D | 0.846 | deleterious | None | None | None | None | N |
| I/H | 0.9989 | likely_pathogenic | 0.9985 | pathogenic | -3.27 | Highly Destabilizing | 0.998 | D | 0.865 | deleterious | None | None | None | None | N |
| I/K | 0.9973 | likely_pathogenic | 0.996 | pathogenic | -2.626 | Highly Destabilizing | 0.966 | D | 0.833 | deleterious | D | 0.539014362 | None | None | N |
| I/L | 0.21 | likely_benign | 0.218 | benign | -1.61 | Destabilizing | 0.002 | N | 0.273 | neutral | N | 0.467748911 | None | None | N |
| I/M | 0.5137 | ambiguous | 0.481 | ambiguous | -1.754 | Destabilizing | 0.934 | D | 0.623 | neutral | N | 0.499007191 | None | None | N |
| I/N | 0.9957 | likely_pathogenic | 0.9945 | pathogenic | -3.275 | Highly Destabilizing | 0.991 | D | 0.868 | deleterious | None | None | None | None | N |
| I/P | 0.9938 | likely_pathogenic | 0.9922 | pathogenic | -2.148 | Highly Destabilizing | 0.991 | D | 0.87 | deleterious | None | None | None | None | N |
| I/Q | 0.9975 | likely_pathogenic | 0.9967 | pathogenic | -2.98 | Highly Destabilizing | 0.991 | D | 0.874 | deleterious | None | None | None | None | N |
| I/R | 0.9954 | likely_pathogenic | 0.9936 | pathogenic | -2.485 | Highly Destabilizing | 0.966 | D | 0.865 | deleterious | D | 0.539014362 | None | None | N |
| I/S | 0.9893 | likely_pathogenic | 0.9866 | pathogenic | -3.762 | Highly Destabilizing | 0.974 | D | 0.788 | deleterious | None | None | None | None | N |
| I/T | 0.9022 | likely_pathogenic | 0.8828 | pathogenic | -3.337 | Highly Destabilizing | 0.891 | D | 0.663 | neutral | D | 0.538760873 | None | None | N |
| I/V | 0.1111 | likely_benign | 0.1046 | benign | -2.148 | Highly Destabilizing | 0.267 | N | 0.291 | neutral | N | 0.427931368 | None | None | N |
| I/W | 0.9985 | likely_pathogenic | 0.9981 | pathogenic | -2.301 | Highly Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Y | 0.9963 | likely_pathogenic | 0.995 | pathogenic | -2.235 | Highly Destabilizing | 0.974 | D | 0.761 | 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.