Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25323 | 76192;76193;76194 | chr2:178570165;178570164;178570163 | chr2:179434892;179434891;179434890 |
| N2AB | 23682 | 71269;71270;71271 | chr2:178570165;178570164;178570163 | chr2:179434892;179434891;179434890 |
| N2A | 22755 | 68488;68489;68490 | chr2:178570165;178570164;178570163 | chr2:179434892;179434891;179434890 |
| N2B | 16258 | 48997;48998;48999 | chr2:178570165;178570164;178570163 | chr2:179434892;179434891;179434890 |
| Novex-1 | 16383 | 49372;49373;49374 | chr2:178570165;178570164;178570163 | chr2:179434892;179434891;179434890 |
| Novex-2 | 16450 | 49573;49574;49575 | chr2:178570165;178570164;178570163 | chr2:179434892;179434891;179434890 |
| 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 | rs781058398  |
-2.481 | 0.978 | N | 0.668 | 0.461 | 0.714052572023 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 8.49E-05 | None | 0 | 0 | None | 0 | None | 4E-05 | 0 | 0 |
| V/A | rs781058398 |
-2.481 | 0.978 | N | 0.668 | 0.461 | 0.714052572023 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.43E-05 | 0 | 0 | 0 | 0 |
| V/A | rs781058398 |
-2.481 | 0.978 | N | 0.668 | 0.461 | 0.714052572023 | gnomAD-4.0.0 | 5.12677E-06 | None | None | None | None | N | None | 0 | 5.08751E-05 | None | 0 | 0 | None | 1.56912E-05 | 0 | 0 | 0 | 0 |
| V/F | rs1342869441 |
-1.637 | 0.994 | N | 0.729 | 0.393 | 0.771885699435 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/F | rs1342869441 |
-1.637 | 0.994 | N | 0.729 | 0.393 | 0.771885699435 | gnomAD-4.0.0 | 1.59178E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43295E-05 | 0 |
| V/G | rs781058398 |
None | 0.999 | D | 0.887 | 0.583 | 0.872732203694 | gnomAD-4.0.0 | 1.59175E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85917E-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 | 0.6155 | likely_pathogenic | 0.6375 | pathogenic | -2.174 | Highly Destabilizing | 0.978 | D | 0.668 | neutral | N | 0.521014423 | None | None | N |
| V/C | 0.9276 | likely_pathogenic | 0.9377 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| V/D | 0.9989 | likely_pathogenic | 0.9985 | pathogenic | -3.222 | Highly Destabilizing | 0.999 | D | 0.898 | deleterious | D | 0.53354927 | None | None | N |
| V/E | 0.9958 | likely_pathogenic | 0.9947 | pathogenic | -2.893 | Highly Destabilizing | 0.999 | D | 0.863 | deleterious | None | None | None | None | N |
| V/F | 0.8943 | likely_pathogenic | 0.895 | pathogenic | -1.255 | Destabilizing | 0.994 | D | 0.729 | prob.delet. | N | 0.508897649 | None | None | N |
| V/G | 0.9215 | likely_pathogenic | 0.9152 | pathogenic | -2.782 | Highly Destabilizing | 0.999 | D | 0.887 | deleterious | D | 0.53354927 | None | None | N |
| V/H | 0.9984 | likely_pathogenic | 0.9983 | pathogenic | -2.79 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| V/I | 0.0901 | likely_benign | 0.1021 | benign | -0.397 | Destabilizing | 0.37 | N | 0.257 | neutral | N | 0.488657327 | None | None | N |
| V/K | 0.9968 | likely_pathogenic | 0.9962 | pathogenic | -1.793 | Destabilizing | 0.999 | D | 0.862 | deleterious | None | None | None | None | N |
| V/L | 0.2808 | likely_benign | 0.3476 | ambiguous | -0.397 | Destabilizing | 0.121 | N | 0.315 | neutral | N | 0.400893909 | None | None | N |
| V/M | 0.5523 | ambiguous | 0.6014 | pathogenic | -0.564 | Destabilizing | 0.995 | D | 0.651 | neutral | None | None | None | None | N |
| V/N | 0.9948 | likely_pathogenic | 0.9944 | pathogenic | -2.538 | Highly Destabilizing | 0.999 | D | 0.902 | deleterious | None | None | None | None | N |
| V/P | 0.9934 | likely_pathogenic | 0.994 | pathogenic | -0.972 | Destabilizing | 0.999 | D | 0.869 | deleterious | None | None | None | None | N |
| V/Q | 0.9941 | likely_pathogenic | 0.9932 | pathogenic | -2.138 | Highly Destabilizing | 0.999 | D | 0.881 | deleterious | None | None | None | None | N |
| V/R | 0.9934 | likely_pathogenic | 0.9923 | pathogenic | -1.99 | Destabilizing | 0.999 | D | 0.903 | deleterious | None | None | None | None | N |
| V/S | 0.9515 | likely_pathogenic | 0.9506 | pathogenic | -2.981 | Highly Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| V/T | 0.7937 | likely_pathogenic | 0.8099 | pathogenic | -2.491 | Highly Destabilizing | 0.992 | D | 0.67 | neutral | None | None | None | None | N |
| V/W | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -1.851 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| V/Y | 0.9949 | likely_pathogenic | 0.9945 | pathogenic | -1.492 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | 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.