Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16724 | 50395;50396;50397 | chr2:178612355;178612354;178612353 | chr2:179477082;179477081;179477080 |
| N2AB | 15083 | 45472;45473;45474 | chr2:178612355;178612354;178612353 | chr2:179477082;179477081;179477080 |
| N2A | 14156 | 42691;42692;42693 | chr2:178612355;178612354;178612353 | chr2:179477082;179477081;179477080 |
| N2B | 7659 | 23200;23201;23202 | chr2:178612355;178612354;178612353 | chr2:179477082;179477081;179477080 |
| Novex-1 | 7784 | 23575;23576;23577 | chr2:178612355;178612354;178612353 | chr2:179477082;179477081;179477080 |
| Novex-2 | 7851 | 23776;23777;23778 | chr2:178612355;178612354;178612353 | chr2:179477082;179477081;179477080 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs768793035  |
-1.223 | 1.0 | D | 0.755 | 0.501 | 0.356484672536 | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.85E-06 | 1.41084E-04 |
| R/Q | rs768793035 |
-1.223 | 1.0 | D | 0.755 | 0.501 | 0.356484672536 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs768793035 |
-1.223 | 1.0 | D | 0.755 | 0.501 | 0.356484672536 | gnomAD-4.0.0 | 2.3568E-05 | None | None | None | None | N | None | 4.01027E-05 | 0 | None | 0 | 0 | None | 0 | 1.64745E-04 | 2.88337E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9958 | likely_pathogenic | 0.9981 | pathogenic | -2.068 | Highly Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | N |
| R/C | 0.9369 | likely_pathogenic | 0.9657 | pathogenic | -1.876 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| R/D | 0.9995 | likely_pathogenic | 0.9998 | pathogenic | -1.346 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| R/E | 0.9939 | likely_pathogenic | 0.9973 | pathogenic | -1.124 | Destabilizing | 0.999 | D | 0.649 | neutral | None | None | None | None | N |
| R/F | 0.9989 | likely_pathogenic | 0.9996 | pathogenic | -1.078 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.9943 | likely_pathogenic | 0.9975 | pathogenic | -2.38 | Highly Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.751949724 | None | None | N |
| R/H | 0.8956 | likely_pathogenic | 0.9406 | pathogenic | -2.137 | Highly Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/I | 0.994 | likely_pathogenic | 0.9979 | pathogenic | -1.141 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| R/K | 0.7685 | likely_pathogenic | 0.8913 | pathogenic | -1.285 | Destabilizing | 0.998 | D | 0.646 | neutral | None | None | None | None | N |
| R/L | 0.9865 | likely_pathogenic | 0.9938 | pathogenic | -1.141 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.656972865 | None | None | N |
| R/M | 0.9964 | likely_pathogenic | 0.999 | pathogenic | -1.677 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/N | 0.9987 | likely_pathogenic | 0.9995 | pathogenic | -1.534 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/P | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.8 | deleterious | D | 0.786329146 | None | None | N |
| R/Q | 0.8934 | likely_pathogenic | 0.9434 | pathogenic | -1.251 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.616602158 | None | None | N |
| R/S | 0.998 | likely_pathogenic | 0.999 | pathogenic | -2.246 | Highly Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| R/T | 0.9968 | likely_pathogenic | 0.9989 | pathogenic | -1.831 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| R/V | 0.9933 | likely_pathogenic | 0.9975 | pathogenic | -1.444 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/W | 0.9859 | likely_pathogenic | 0.9932 | pathogenic | -0.714 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| R/Y | 0.9959 | likely_pathogenic | 0.9983 | pathogenic | -0.642 | Destabilizing | 1.0 | D | 0.831 | 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.