Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30900 | 92923;92924;92925 | chr2:178548928;178548927;178548926 | chr2:179413655;179413654;179413653 |
| N2AB | 29259 | 88000;88001;88002 | chr2:178548928;178548927;178548926 | chr2:179413655;179413654;179413653 |
| N2A | 28332 | 85219;85220;85221 | chr2:178548928;178548927;178548926 | chr2:179413655;179413654;179413653 |
| N2B | 21835 | 65728;65729;65730 | chr2:178548928;178548927;178548926 | chr2:179413655;179413654;179413653 |
| Novex-1 | 21960 | 66103;66104;66105 | chr2:178548928;178548927;178548926 | chr2:179413655;179413654;179413653 |
| Novex-2 | 22027 | 66304;66305;66306 | chr2:178548928;178548927;178548926 | chr2:179413655;179413654;179413653 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1452525804  |
-2.133 | 0.999 | N | 0.59 | 0.594 | 0.264547087235 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| N/D | rs1452525804 |
-2.133 | 0.999 | N | 0.59 | 0.594 | 0.264547087235 | gnomAD-4.0.0 | 1.36836E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87308E-05 | 0 | 8.99433E-07 | 0 | 0 |
| N/S | rs186234393 |
-1.248 | 0.999 | N | 0.571 | 0.496 | None | gnomAD-2.1.1 | 3.31873E-04 | None | None | None | None | N | None | 0 | 8.48E-05 | None | 0 | 4.40754E-03 | None | 0 | None | 0 | 0 | 5.6164E-04 |
| N/S | rs186234393 |
-1.248 | 0.999 | N | 0.571 | 0.496 | None | gnomAD-3.1.2 | 1.64271E-04 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 4.24547E-03 | None | 0 | 0 | 0 | 0 | 9.5511E-04 |
| N/S | rs186234393 |
-1.248 | 0.999 | N | 0.571 | 0.496 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 4E-03 | 0 | None | None | None | 0 | None |
| N/S | rs186234393 |
-1.248 | 0.999 | N | 0.571 | 0.496 | None | gnomAD-4.0.0 | 9.72786E-05 | None | None | None | None | N | None | 1.33223E-05 | 4.9985E-05 | None | 0 | 2.22896E-03 | None | 0 | 0 | 5.08551E-06 | 2.19568E-05 | 7.20184E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.971 | likely_pathogenic | 0.9808 | pathogenic | -0.865 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| N/C | 0.8328 | likely_pathogenic | 0.8722 | pathogenic | -0.515 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| N/D | 0.9677 | likely_pathogenic | 0.9768 | pathogenic | -2.041 | Highly Destabilizing | 0.999 | D | 0.59 | neutral | N | 0.517043815 | None | None | N |
| N/E | 0.9959 | likely_pathogenic | 0.9975 | pathogenic | -1.854 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| N/F | 0.9975 | likely_pathogenic | 0.9985 | pathogenic | -0.507 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| N/G | 0.9415 | likely_pathogenic | 0.9613 | pathogenic | -1.221 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| N/H | 0.9125 | likely_pathogenic | 0.9371 | pathogenic | -0.886 | Destabilizing | 1.0 | D | 0.769 | deleterious | D | 0.547304524 | None | None | N |
| N/I | 0.9747 | likely_pathogenic | 0.9826 | pathogenic | 0.063 | Stabilizing | 1.0 | D | 0.779 | deleterious | D | 0.547811503 | None | None | N |
| N/K | 0.9955 | likely_pathogenic | 0.9972 | pathogenic | -0.444 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.531313409 | None | None | N |
| N/L | 0.9346 | likely_pathogenic | 0.9566 | pathogenic | 0.063 | Stabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | N |
| N/M | 0.9823 | likely_pathogenic | 0.988 | pathogenic | 0.292 | Stabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| N/P | 0.9853 | likely_pathogenic | 0.9898 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| N/Q | 0.994 | likely_pathogenic | 0.9957 | pathogenic | -1.181 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| N/R | 0.988 | likely_pathogenic | 0.9921 | pathogenic | -0.528 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| N/S | 0.4032 | ambiguous | 0.4848 | ambiguous | -1.271 | Destabilizing | 0.999 | D | 0.571 | neutral | N | 0.50435761 | None | None | N |
| N/T | 0.8057 | likely_pathogenic | 0.8431 | pathogenic | -0.921 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.507520707 | None | None | N |
| N/V | 0.9669 | likely_pathogenic | 0.9764 | pathogenic | -0.219 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| N/W | 0.9988 | likely_pathogenic | 0.9993 | pathogenic | -0.47 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| N/Y | 0.9773 | likely_pathogenic | 0.9854 | pathogenic | -0.104 | Destabilizing | 1.0 | D | 0.792 | deleterious | D | 0.558660829 | 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.