Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2846 | 8761;8762;8763 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
| N2AB | 2846 | 8761;8762;8763 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
| N2A | 2846 | 8761;8762;8763 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
| N2B | 2800 | 8623;8624;8625 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
| Novex-1 | 2800 | 8623;8624;8625 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
| Novex-2 | 2800 | 8623;8624;8625 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
| Novex-3 | 2846 | 8761;8762;8763 | chr2:178770165;178770164;178770163 | chr2:179634892;179634891;179634890 |
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 | rs1658158334  |
None | 0.543 | N | 0.285 | 0.263 | 0.112648838833 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs1658158334 |
None | 0.543 | N | 0.285 | 0.263 | 0.112648838833 | gnomAD-4.0.0 | 2.02991E-06 | None | None | None | None | N | None | 1.74801E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.2049E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9179 | likely_pathogenic | 0.9403 | pathogenic | 0.115 | Stabilizing | 0.992 | D | 0.498 | neutral | None | None | None | None | N |
| R/C | 0.7315 | likely_pathogenic | 0.7634 | pathogenic | -0.096 | Destabilizing | 1.0 | D | 0.61 | neutral | None | None | None | None | N |
| R/D | 0.9496 | likely_pathogenic | 0.9556 | pathogenic | -0.221 | Destabilizing | 0.999 | D | 0.49 | neutral | None | None | None | None | N |
| R/E | 0.8459 | likely_pathogenic | 0.8675 | pathogenic | -0.165 | Destabilizing | 0.992 | D | 0.463 | neutral | None | None | None | None | N |
| R/F | 0.9602 | likely_pathogenic | 0.9737 | pathogenic | -0.131 | Destabilizing | 1.0 | D | 0.553 | neutral | None | None | None | None | N |
| R/G | 0.567 | likely_pathogenic | 0.611 | pathogenic | -0.06 | Destabilizing | 0.994 | D | 0.411 | neutral | N | 0.377776528 | None | None | N |
| R/H | 0.4067 | ambiguous | 0.4586 | ambiguous | -0.592 | Destabilizing | 1.0 | D | 0.495 | neutral | None | None | None | None | N |
| R/I | 0.9316 | likely_pathogenic | 0.9594 | pathogenic | 0.536 | Stabilizing | 1.0 | D | 0.559 | neutral | None | None | None | None | N |
| R/K | 0.2542 | likely_benign | 0.2963 | benign | -0.033 | Destabilizing | 0.543 | D | 0.285 | neutral | N | 0.430993086 | None | None | N |
| R/L | 0.8259 | likely_pathogenic | 0.8665 | pathogenic | 0.536 | Stabilizing | 0.996 | D | 0.411 | neutral | None | None | None | None | N |
| R/M | 0.8277 | likely_pathogenic | 0.8893 | pathogenic | 0.052 | Stabilizing | 1.0 | D | 0.473 | neutral | N | 0.491985656 | None | None | N |
| R/N | 0.9181 | likely_pathogenic | 0.9284 | pathogenic | 0.119 | Stabilizing | 0.999 | D | 0.455 | neutral | None | None | None | None | N |
| R/P | 0.9676 | likely_pathogenic | 0.9774 | pathogenic | 0.415 | Stabilizing | 1.0 | D | 0.497 | neutral | None | None | None | None | N |
| R/Q | 0.3461 | ambiguous | 0.3831 | ambiguous | 0.064 | Stabilizing | 0.998 | D | 0.46 | neutral | None | None | None | None | N |
| R/S | 0.936 | likely_pathogenic | 0.9488 | pathogenic | -0.097 | Destabilizing | 0.989 | D | 0.464 | neutral | N | 0.443608273 | None | None | N |
| R/T | 0.9095 | likely_pathogenic | 0.9379 | pathogenic | 0.079 | Stabilizing | 0.998 | D | 0.441 | neutral | N | 0.448982622 | None | None | N |
| R/V | 0.9484 | likely_pathogenic | 0.9654 | pathogenic | 0.415 | Stabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | N |
| R/W | 0.6274 | likely_pathogenic | 0.6994 | pathogenic | -0.267 | Destabilizing | 1.0 | D | 0.632 | neutral | N | 0.493429591 | None | None | N |
| R/Y | 0.8813 | likely_pathogenic | 0.904 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.502 | 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.