Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18784 | 56575;56576;56577 | chr2:178599443;178599442;178599441 | chr2:179464170;179464169;179464168 |
| N2AB | 17143 | 51652;51653;51654 | chr2:178599443;178599442;178599441 | chr2:179464170;179464169;179464168 |
| N2A | 16216 | 48871;48872;48873 | chr2:178599443;178599442;178599441 | chr2:179464170;179464169;179464168 |
| N2B | 9719 | 29380;29381;29382 | chr2:178599443;178599442;178599441 | chr2:179464170;179464169;179464168 |
| Novex-1 | 9844 | 29755;29756;29757 | chr2:178599443;178599442;178599441 | chr2:179464170;179464169;179464168 |
| Novex-2 | 9911 | 29956;29957;29958 | chr2:178599443;178599442;178599441 | chr2:179464170;179464169;179464168 |
| 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/C | rs774740211  |
-0.428 | 1.0 | N | 0.857 | 0.444 | 0.515715180578 | gnomAD-2.1.1 | 5.61E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.14E-05 | 0 |
| R/C | rs774740211 |
-0.428 | 1.0 | N | 0.857 | 0.444 | 0.515715180578 | gnomAD-4.0.0 | 5.11012E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.53973E-06 | 0 | 0 |
| R/H | rs771284532 |
-1.113 | 1.0 | N | 0.604 | 0.29 | 0.245660935333 | gnomAD-2.1.1 | 6.97E-05 | None | None | None | None | N | None | 0 | 1.72563E-04 | None | 0 | 0 | None | 6.26E-05 | None | 4.68E-05 | 8.61E-05 | 0 |
| R/H | rs771284532 |
-1.113 | 1.0 | N | 0.604 | 0.29 | 0.245660935333 | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 0 | 1.96747E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| R/H | rs771284532 |
-1.113 | 1.0 | N | 0.604 | 0.29 | 0.245660935333 | gnomAD-4.0.0 | 4.97203E-05 | None | None | None | None | N | None | 1.3926E-05 | 1.49381E-04 | None | 4.05449E-05 | 0 | None | 1.63768E-05 | 1.75316E-04 | 4.99474E-05 | 6.76498E-05 | 5.10378E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5637 | ambiguous | 0.5082 | ambiguous | -0.261 | Destabilizing | 0.968 | D | 0.578 | neutral | None | None | None | None | N |
| R/C | 0.1705 | likely_benign | 0.1488 | benign | -0.345 | Destabilizing | 1.0 | D | 0.857 | deleterious | N | 0.493243751 | None | None | N |
| R/D | 0.8993 | likely_pathogenic | 0.8668 | pathogenic | -0.037 | Destabilizing | 0.995 | D | 0.561 | neutral | None | None | None | None | N |
| R/E | 0.5714 | likely_pathogenic | 0.5274 | ambiguous | 0.044 | Stabilizing | 0.984 | D | 0.571 | neutral | None | None | None | None | N |
| R/F | 0.6494 | likely_pathogenic | 0.5857 | pathogenic | -0.387 | Destabilizing | 0.998 | D | 0.774 | deleterious | None | None | None | None | N |
| R/G | 0.5482 | ambiguous | 0.4824 | ambiguous | -0.49 | Destabilizing | 0.992 | D | 0.607 | neutral | N | 0.492736771 | None | None | N |
| R/H | 0.1577 | likely_benign | 0.1433 | benign | -0.926 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.470113066 | None | None | N |
| R/I | 0.2575 | likely_benign | 0.2233 | benign | 0.321 | Stabilizing | 0.998 | D | 0.801 | deleterious | None | None | None | None | N |
| R/K | 0.1045 | likely_benign | 0.1033 | benign | -0.313 | Destabilizing | 0.962 | D | 0.5 | neutral | None | None | None | None | N |
| R/L | 0.3068 | likely_benign | 0.2621 | benign | 0.321 | Stabilizing | 0.992 | D | 0.575 | neutral | N | 0.494494716 | None | None | N |
| R/M | 0.3714 | ambiguous | 0.3283 | benign | -0.063 | Destabilizing | 1.0 | D | 0.616 | neutral | None | None | None | None | N |
| R/N | 0.7694 | likely_pathogenic | 0.7189 | pathogenic | 0.019 | Stabilizing | 0.998 | D | 0.591 | neutral | None | None | None | None | N |
| R/P | 0.4347 | ambiguous | 0.424 | ambiguous | 0.148 | Stabilizing | 0.071 | N | 0.413 | neutral | N | 0.456589689 | None | None | N |
| R/Q | 0.1393 | likely_benign | 0.1279 | benign | -0.119 | Destabilizing | 0.998 | D | 0.63 | neutral | None | None | None | None | N |
| R/S | 0.7084 | likely_pathogenic | 0.6516 | pathogenic | -0.482 | Destabilizing | 0.992 | D | 0.676 | prob.neutral | N | 0.462769232 | None | None | N |
| R/T | 0.4086 | ambiguous | 0.3511 | ambiguous | -0.25 | Destabilizing | 0.984 | D | 0.656 | prob.neutral | None | None | None | None | N |
| R/V | 0.3586 | ambiguous | 0.3214 | benign | 0.148 | Stabilizing | 0.995 | D | 0.625 | neutral | None | None | None | None | N |
| R/W | 0.3381 | likely_benign | 0.2771 | benign | -0.311 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| R/Y | 0.5101 | ambiguous | 0.4525 | ambiguous | 0.063 | Stabilizing | 0.998 | D | 0.821 | 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.