Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31171 | 93736;93737;93738 | chr2:178548115;178548114;178548113 | chr2:179412842;179412841;179412840 |
| N2AB | 29530 | 88813;88814;88815 | chr2:178548115;178548114;178548113 | chr2:179412842;179412841;179412840 |
| N2A | 28603 | 86032;86033;86034 | chr2:178548115;178548114;178548113 | chr2:179412842;179412841;179412840 |
| N2B | 22106 | 66541;66542;66543 | chr2:178548115;178548114;178548113 | chr2:179412842;179412841;179412840 |
| Novex-1 | 22231 | 66916;66917;66918 | chr2:178548115;178548114;178548113 | chr2:179412842;179412841;179412840 |
| Novex-2 | 22298 | 67117;67118;67119 | chr2:178548115;178548114;178548113 | chr2:179412842;179412841;179412840 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/C | rs759179376  |
-1.212 | 0.946 | N | 0.596 | 0.31 | 0.606262950116 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| F/C | rs759179376 |
-1.212 | 0.946 | N | 0.596 | 0.31 | 0.606262950116 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/C | rs759179376 |
-1.212 | 0.946 | N | 0.596 | 0.31 | 0.606262950116 | gnomAD-4.0.0 | 1.85902E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5428E-06 | 0 | 0 |
| F/L | None | None | None | N | 0.177 | 0.177 | 0.181679512989 | gnomAD-4.0.0 | 3.18218E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.4108E-04 | 2.85806E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.4569 | ambiguous | 0.5134 | ambiguous | -2.071 | Highly Destabilizing | 0.104 | N | 0.513 | neutral | None | None | None | None | I |
| F/C | 0.1646 | likely_benign | 0.1905 | benign | -1.247 | Destabilizing | 0.946 | D | 0.596 | neutral | N | 0.449525723 | None | None | I |
| F/D | 0.8821 | likely_pathogenic | 0.8859 | pathogenic | -0.808 | Destabilizing | 0.859 | D | 0.616 | neutral | None | None | None | None | I |
| F/E | 0.878 | likely_pathogenic | 0.8894 | pathogenic | -0.65 | Destabilizing | 0.667 | D | 0.632 | neutral | None | None | None | None | I |
| F/G | 0.7164 | likely_pathogenic | 0.7383 | pathogenic | -2.465 | Highly Destabilizing | 0.364 | N | 0.578 | neutral | None | None | None | None | I |
| F/H | 0.4608 | ambiguous | 0.5091 | ambiguous | -0.749 | Destabilizing | 0.497 | N | 0.57 | neutral | None | None | None | None | I |
| F/I | 0.2113 | likely_benign | 0.2384 | benign | -0.86 | Destabilizing | 0.042 | N | 0.437 | neutral | N | 0.485465093 | None | None | I |
| F/K | 0.8043 | likely_pathogenic | 0.8278 | pathogenic | -1.21 | Destabilizing | 0.364 | N | 0.609 | neutral | None | None | None | None | I |
| F/L | 0.6612 | likely_pathogenic | 0.7296 | pathogenic | -0.86 | Destabilizing | None | N | 0.177 | neutral | N | 0.455256829 | None | None | I |
| F/M | 0.3174 | likely_benign | 0.3528 | ambiguous | -0.718 | Destabilizing | 0.011 | N | 0.203 | neutral | None | None | None | None | I |
| F/N | 0.7303 | likely_pathogenic | 0.7638 | pathogenic | -1.412 | Destabilizing | 0.667 | D | 0.616 | neutral | None | None | None | None | I |
| F/P | 0.9967 | likely_pathogenic | 0.9973 | pathogenic | -1.262 | Destabilizing | 0.859 | D | 0.613 | neutral | None | None | None | None | I |
| F/Q | 0.7177 | likely_pathogenic | 0.7466 | pathogenic | -1.355 | Destabilizing | 0.667 | D | 0.616 | neutral | None | None | None | None | I |
| F/R | 0.704 | likely_pathogenic | 0.7198 | pathogenic | -0.766 | Destabilizing | 0.667 | D | 0.616 | neutral | None | None | None | None | I |
| F/S | 0.4497 | ambiguous | 0.5029 | ambiguous | -2.281 | Highly Destabilizing | 0.301 | N | 0.552 | neutral | N | 0.46780084 | None | None | I |
| F/T | 0.5307 | ambiguous | 0.5921 | pathogenic | -2.022 | Highly Destabilizing | 0.22 | N | 0.542 | neutral | None | None | None | None | I |
| F/V | 0.1883 | likely_benign | 0.2142 | benign | -1.262 | Destabilizing | 0.042 | N | 0.492 | neutral | N | 0.477880186 | None | None | I |
| F/W | 0.4594 | ambiguous | 0.4614 | ambiguous | 0.186 | Stabilizing | 0.667 | D | 0.529 | neutral | None | None | None | None | I |
| F/Y | 0.1137 | likely_benign | 0.121 | benign | -0.118 | Destabilizing | 0.001 | N | 0.187 | neutral | N | 0.420757467 | None | None | I |
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.