Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16499 | 49720;49721;49722 | chr2:178613788;178613787;178613786 | chr2:179478515;179478514;179478513 |
| N2AB | 14858 | 44797;44798;44799 | chr2:178613788;178613787;178613786 | chr2:179478515;179478514;179478513 |
| N2A | 13931 | 42016;42017;42018 | chr2:178613788;178613787;178613786 | chr2:179478515;179478514;179478513 |
| N2B | 7434 | 22525;22526;22527 | chr2:178613788;178613787;178613786 | chr2:179478515;179478514;179478513 |
| Novex-1 | 7559 | 22900;22901;22902 | chr2:178613788;178613787;178613786 | chr2:179478515;179478514;179478513 |
| Novex-2 | 7626 | 23101;23102;23103 | chr2:178613788;178613787;178613786 | chr2:179478515;179478514;179478513 |
| 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/K | None | None | None | N | 0.165 | 0.08 | 0.143124449307 | gnomAD-4.0.0 | 5.47764E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.20033E-06 | 0 | 0 |
| R/T | rs1479161212  |
-0.18 | 0.324 | N | 0.551 | 0.14 | 0.243972157842 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/T | rs1479161212 |
-0.18 | 0.324 | N | 0.551 | 0.14 | 0.243972157842 | gnomAD-4.0.0 | 6.84705E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16025E-05 | 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 | 0.8696 | likely_pathogenic | 0.8927 | pathogenic | -0.759 | Destabilizing | 0.116 | N | 0.534 | neutral | None | None | None | None | N |
| R/C | 0.5621 | ambiguous | 0.5906 | pathogenic | -0.549 | Destabilizing | 0.981 | D | 0.641 | neutral | None | None | None | None | N |
| R/D | 0.978 | likely_pathogenic | 0.9803 | pathogenic | -0.021 | Destabilizing | 0.388 | N | 0.61 | neutral | None | None | None | None | N |
| R/E | 0.8893 | likely_pathogenic | 0.9107 | pathogenic | 0.138 | Stabilizing | 0.116 | N | 0.532 | neutral | None | None | None | None | N |
| R/F | 0.9138 | likely_pathogenic | 0.9278 | pathogenic | -0.393 | Destabilizing | 0.932 | D | 0.639 | neutral | None | None | None | None | N |
| R/G | 0.8825 | likely_pathogenic | 0.8975 | pathogenic | -1.108 | Destabilizing | 0.324 | N | 0.574 | neutral | N | 0.46906457 | None | None | N |
| R/H | 0.4034 | ambiguous | 0.4254 | ambiguous | -1.563 | Destabilizing | 0.818 | D | 0.56 | neutral | None | None | None | None | N |
| R/I | 0.6477 | likely_pathogenic | 0.7181 | pathogenic | 0.194 | Stabilizing | 0.773 | D | 0.644 | neutral | N | 0.48194747 | None | None | N |
| R/K | 0.162 | likely_benign | 0.1761 | benign | -0.607 | Destabilizing | None | N | 0.165 | neutral | N | 0.438375646 | None | None | N |
| R/L | 0.5996 | likely_pathogenic | 0.6308 | pathogenic | 0.194 | Stabilizing | 0.388 | N | 0.574 | neutral | None | None | None | None | N |
| R/M | 0.7152 | likely_pathogenic | 0.7764 | pathogenic | -0.24 | Destabilizing | 0.932 | D | 0.613 | neutral | None | None | None | None | N |
| R/N | 0.9497 | likely_pathogenic | 0.9577 | pathogenic | -0.197 | Destabilizing | 0.388 | N | 0.521 | neutral | None | None | None | None | N |
| R/P | 0.7361 | likely_pathogenic | 0.7537 | pathogenic | -0.103 | Destabilizing | 0.818 | D | 0.621 | neutral | None | None | None | None | N |
| R/Q | 0.3563 | ambiguous | 0.3956 | ambiguous | -0.24 | Destabilizing | 0.241 | N | 0.537 | neutral | None | None | None | None | N |
| R/S | 0.9401 | likely_pathogenic | 0.9513 | pathogenic | -0.905 | Destabilizing | 0.193 | N | 0.538 | neutral | N | 0.478120782 | None | None | N |
| R/T | 0.7896 | likely_pathogenic | 0.8339 | pathogenic | -0.543 | Destabilizing | 0.324 | N | 0.551 | neutral | N | 0.47099916 | None | None | N |
| R/V | 0.7209 | likely_pathogenic | 0.7639 | pathogenic | -0.103 | Destabilizing | 0.69 | D | 0.605 | neutral | None | None | None | None | N |
| R/W | 0.6318 | likely_pathogenic | 0.6906 | pathogenic | -0.069 | Destabilizing | 0.981 | D | 0.665 | neutral | None | None | None | None | N |
| R/Y | 0.8489 | likely_pathogenic | 0.8736 | pathogenic | 0.192 | Stabilizing | 0.932 | D | 0.646 | neutral | 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.