Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20827 | 62704;62705;62706 | chr2:178589246;178589245;178589244 | chr2:179453973;179453972;179453971 |
| N2AB | 19186 | 57781;57782;57783 | chr2:178589246;178589245;178589244 | chr2:179453973;179453972;179453971 |
| N2A | 18259 | 55000;55001;55002 | chr2:178589246;178589245;178589244 | chr2:179453973;179453972;179453971 |
| N2B | 11762 | 35509;35510;35511 | chr2:178589246;178589245;178589244 | chr2:179453973;179453972;179453971 |
| Novex-1 | 11887 | 35884;35885;35886 | chr2:178589246;178589245;178589244 | chr2:179453973;179453972;179453971 |
| Novex-2 | 11954 | 36085;36086;36087 | chr2:178589246;178589245;178589244 | chr2:179453973;179453972;179453971 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | rs1001628726  |
None | 0.999 | N | 0.77 | 0.44 | 0.273938319068 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.20627E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78927E-04 |
| S/P | rs1001628726 |
None | 0.999 | N | 0.77 | 0.44 | 0.273938319068 | gnomAD-4.0.0 | 8.05767E-06 | None | None | None | None | N | None | 1.20147E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69547E-06 | 1.09794E-05 | 1.60149E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1306 | likely_benign | 0.1443 | benign | -0.924 | Destabilizing | 0.973 | D | 0.579 | neutral | N | 0.508560092 | None | None | N |
| S/C | 0.1031 | likely_benign | 0.1318 | benign | -0.83 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.514603417 | None | None | N |
| S/D | 0.9833 | likely_pathogenic | 0.987 | pathogenic | -1.413 | Destabilizing | 0.996 | D | 0.654 | neutral | None | None | None | None | N |
| S/E | 0.9873 | likely_pathogenic | 0.9899 | pathogenic | -1.251 | Destabilizing | 0.996 | D | 0.648 | neutral | None | None | None | None | N |
| S/F | 0.8712 | likely_pathogenic | 0.887 | pathogenic | -0.889 | Destabilizing | 0.999 | D | 0.791 | deleterious | N | 0.497407579 | None | None | N |
| S/G | 0.3571 | ambiguous | 0.3693 | ambiguous | -1.293 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| S/H | 0.9425 | likely_pathogenic | 0.9492 | pathogenic | -1.642 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| S/I | 0.6043 | likely_pathogenic | 0.6758 | pathogenic | None | Stabilizing | 0.998 | D | 0.796 | deleterious | None | None | None | None | N |
| S/K | 0.9972 | likely_pathogenic | 0.9976 | pathogenic | -0.367 | Destabilizing | 0.996 | D | 0.65 | neutral | None | None | None | None | N |
| S/L | 0.3891 | ambiguous | 0.4211 | ambiguous | None | Stabilizing | 0.992 | D | 0.708 | prob.delet. | None | None | None | None | N |
| S/M | 0.5164 | ambiguous | 0.5643 | pathogenic | 0.035 | Stabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| S/N | 0.831 | likely_pathogenic | 0.8631 | pathogenic | -1.0 | Destabilizing | 0.996 | D | 0.658 | neutral | None | None | None | None | N |
| S/P | 0.9871 | likely_pathogenic | 0.9915 | pathogenic | -0.274 | Destabilizing | 0.999 | D | 0.77 | deleterious | N | 0.467595078 | None | None | N |
| S/Q | 0.9662 | likely_pathogenic | 0.9724 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| S/R | 0.9947 | likely_pathogenic | 0.9953 | pathogenic | -0.621 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | N |
| S/T | 0.0812 | likely_benign | 0.0898 | benign | -0.731 | Destabilizing | 0.543 | D | 0.505 | neutral | N | 0.470119134 | None | None | N |
| S/V | 0.3878 | ambiguous | 0.4537 | ambiguous | -0.274 | Destabilizing | 0.998 | D | 0.754 | deleterious | None | None | None | None | N |
| S/W | 0.9508 | likely_pathogenic | 0.9555 | pathogenic | -1.046 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| S/Y | 0.8998 | likely_pathogenic | 0.9137 | pathogenic | -0.635 | Destabilizing | 0.999 | D | 0.79 | deleterious | N | 0.460060207 | 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.