Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32295 | 97108;97109;97110 | chr2:178543090;178543089;178543088 | chr2:179407817;179407816;179407815 |
| N2AB | 30654 | 92185;92186;92187 | chr2:178543090;178543089;178543088 | chr2:179407817;179407816;179407815 |
| N2A | 29727 | 89404;89405;89406 | chr2:178543090;178543089;178543088 | chr2:179407817;179407816;179407815 |
| N2B | 23230 | 69913;69914;69915 | chr2:178543090;178543089;178543088 | chr2:179407817;179407816;179407815 |
| Novex-1 | 23355 | 70288;70289;70290 | chr2:178543090;178543089;178543088 | chr2:179407817;179407816;179407815 |
| Novex-2 | 23422 | 70489;70490;70491 | chr2:178543090;178543089;178543088 | chr2:179407817;179407816;179407815 |
| 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/M | rs199532781  |
-0.386 | 1.0 | N | 0.789 | 0.277 | None | gnomAD-2.1.1 | 7.67E-05 | None | None | None | None | N | None | 1.66486E-04 | 0 | None | 0 | 2.56358E-04 | None | 2.05226E-04 | None | 0 | 4.79E-05 | 0 |
| V/M | rs199532781 |
-0.386 | 1.0 | N | 0.789 | 0.277 | None | gnomAD-3.1.2 | 7.96E-05 | None | None | None | None | N | None | 1.71518E-04 | 0 | 0 | 0 | 1.94326E-04 | None | 0 | 0 | 4.42E-05 | 2.09118E-04 | 0 |
| V/M | rs199532781 |
-0.386 | 1.0 | N | 0.789 | 0.277 | None | gnomAD-4.0.0 | 7.0152E-05 | None | None | None | None | N | None | 1.21379E-04 | 3.3627E-05 | None | 0 | 1.34747E-04 | None | 1.60205E-05 | 1.66556E-04 | 5.81821E-05 | 2.56662E-04 | 3.23729E-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 | 0.5457 | ambiguous | 0.4789 | ambiguous | -1.713 | Destabilizing | 0.998 | D | 0.573 | neutral | N | 0.503610368 | None | None | N |
| V/C | 0.8952 | likely_pathogenic | 0.8677 | pathogenic | -1.235 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| V/D | 0.9355 | likely_pathogenic | 0.9231 | pathogenic | -1.923 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| V/E | 0.8225 | likely_pathogenic | 0.7957 | pathogenic | -1.731 | Destabilizing | 1.0 | D | 0.871 | deleterious | N | 0.515220163 | None | None | N |
| V/F | 0.3675 | ambiguous | 0.3233 | benign | -1.019 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| V/G | 0.7213 | likely_pathogenic | 0.6825 | pathogenic | -2.22 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | N | 0.515980631 | None | None | N |
| V/H | 0.922 | likely_pathogenic | 0.9013 | pathogenic | -1.816 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| V/I | 0.0918 | likely_benign | 0.0847 | benign | -0.327 | Destabilizing | 0.446 | N | 0.259 | neutral | None | None | None | None | N |
| V/K | 0.8124 | likely_pathogenic | 0.7911 | pathogenic | -1.4 | Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| V/L | 0.3616 | ambiguous | 0.3178 | benign | -0.327 | Destabilizing | 0.96 | D | 0.553 | neutral | N | 0.491240104 | None | None | N |
| V/M | 0.27 | likely_benign | 0.2233 | benign | -0.35 | Destabilizing | 1.0 | D | 0.789 | deleterious | N | 0.497533981 | None | None | N |
| V/N | 0.8486 | likely_pathogenic | 0.8308 | pathogenic | -1.655 | Destabilizing | 0.999 | D | 0.881 | deleterious | None | None | None | None | N |
| V/P | 0.949 | likely_pathogenic | 0.9381 | pathogenic | -0.759 | Destabilizing | 0.999 | D | 0.877 | deleterious | None | None | None | None | N |
| V/Q | 0.7731 | likely_pathogenic | 0.7426 | pathogenic | -1.526 | Destabilizing | 1.0 | D | 0.893 | deleterious | None | None | None | None | N |
| V/R | 0.7669 | likely_pathogenic | 0.7548 | pathogenic | -1.232 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| V/S | 0.7394 | likely_pathogenic | 0.6983 | pathogenic | -2.291 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| V/T | 0.5258 | ambiguous | 0.4829 | ambiguous | -1.942 | Destabilizing | 0.997 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/W | 0.9579 | likely_pathogenic | 0.9407 | pathogenic | -1.432 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| V/Y | 0.8403 | likely_pathogenic | 0.8028 | pathogenic | -1.017 | Destabilizing | 1.0 | D | 0.859 | 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.