Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17022 | 51289;51290;51291 | chr2:178611065;178611064;178611063 | chr2:179475792;179475791;179475790 |
| N2AB | 15381 | 46366;46367;46368 | chr2:178611065;178611064;178611063 | chr2:179475792;179475791;179475790 |
| N2A | 14454 | 43585;43586;43587 | chr2:178611065;178611064;178611063 | chr2:179475792;179475791;179475790 |
| N2B | 7957 | 24094;24095;24096 | chr2:178611065;178611064;178611063 | chr2:179475792;179475791;179475790 |
| Novex-1 | 8082 | 24469;24470;24471 | chr2:178611065;178611064;178611063 | chr2:179475792;179475791;179475790 |
| Novex-2 | 8149 | 24670;24671;24672 | chr2:178611065;178611064;178611063 | chr2:179475792;179475791;179475790 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs372419267  |
None | 0.946 | D | 0.869 | 0.431 | 0.71113996826 | gnomAD-4.0.0 | 8.215E-06 | None | None | None | None | N | None | 2.9933E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.89873E-06 | 0 | 0 |
| A/V | rs372419267 |
-0.501 | 0.911 | D | 0.633 | 0.398 | None | gnomAD-2.1.1 | 1.07213E-04 | None | None | None | None | N | None | 9.93377E-04 | 1.41587E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40449E-04 |
| A/V | rs372419267 |
-0.501 | 0.911 | D | 0.633 | 0.398 | None | gnomAD-3.1.2 | 4.14632E-04 | None | None | None | None | N | None | 1.42436E-03 | 1.31251E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.79386E-04 |
| A/V | rs372419267 |
-0.501 | 0.911 | D | 0.633 | 0.398 | None | gnomAD-4.0.0 | 6.94444E-05 | None | None | None | None | N | None | 1.3075E-03 | 1.16756E-04 | None | 0 | 0 | None | 1.5623E-05 | 0 | 1.69609E-06 | 0 | 6.408E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5785 | likely_pathogenic | 0.5696 | pathogenic | -0.918 | Destabilizing | 0.998 | D | 0.771 | deleterious | None | None | None | None | N |
| A/D | 0.6066 | likely_pathogenic | 0.6326 | pathogenic | -0.512 | Destabilizing | 0.946 | D | 0.869 | deleterious | D | 0.575857452 | None | None | N |
| A/E | 0.4158 | ambiguous | 0.4438 | ambiguous | -0.579 | Destabilizing | 0.979 | D | 0.852 | deleterious | None | None | None | None | N |
| A/F | 0.593 | likely_pathogenic | 0.6335 | pathogenic | -0.986 | Destabilizing | 0.993 | D | 0.902 | deleterious | None | None | None | None | N |
| A/G | 0.1463 | likely_benign | 0.1406 | benign | -0.955 | Destabilizing | 0.016 | N | 0.337 | neutral | N | 0.505557969 | None | None | N |
| A/H | 0.7046 | likely_pathogenic | 0.707 | pathogenic | -1.005 | Destabilizing | 0.998 | D | 0.88 | deleterious | None | None | None | None | N |
| A/I | 0.5234 | ambiguous | 0.5781 | pathogenic | -0.36 | Destabilizing | 0.979 | D | 0.879 | deleterious | None | None | None | None | N |
| A/K | 0.6669 | likely_pathogenic | 0.6781 | pathogenic | -0.935 | Destabilizing | 0.959 | D | 0.859 | deleterious | None | None | None | None | N |
| A/L | 0.4033 | ambiguous | 0.4286 | ambiguous | -0.36 | Destabilizing | 0.979 | D | 0.754 | deleterious | None | None | None | None | N |
| A/M | 0.3637 | ambiguous | 0.4038 | ambiguous | -0.346 | Destabilizing | 0.998 | D | 0.835 | deleterious | None | None | None | None | N |
| A/N | 0.4807 | ambiguous | 0.4959 | ambiguous | -0.644 | Destabilizing | 0.959 | D | 0.876 | deleterious | None | None | None | None | N |
| A/P | 0.9412 | likely_pathogenic | 0.9236 | pathogenic | -0.449 | Destabilizing | 0.973 | D | 0.88 | deleterious | D | 0.718937384 | None | None | N |
| A/Q | 0.5038 | ambiguous | 0.51 | ambiguous | -0.82 | Destabilizing | 0.979 | D | 0.89 | deleterious | None | None | None | None | N |
| A/R | 0.5754 | likely_pathogenic | 0.567 | pathogenic | -0.591 | Destabilizing | 0.979 | D | 0.879 | deleterious | None | None | None | None | N |
| A/S | 0.1001 | likely_benign | 0.0994 | benign | -1.049 | Destabilizing | 0.716 | D | 0.509 | neutral | N | 0.504730904 | None | None | N |
| A/T | 0.1186 | likely_benign | 0.1256 | benign | -1.012 | Destabilizing | 0.946 | D | 0.683 | prob.neutral | N | 0.512741152 | None | None | N |
| A/V | 0.2847 | likely_benign | 0.3107 | benign | -0.449 | Destabilizing | 0.911 | D | 0.633 | neutral | D | 0.572382952 | None | None | N |
| A/W | 0.9112 | likely_pathogenic | 0.9158 | pathogenic | -1.225 | Destabilizing | 0.998 | D | 0.861 | deleterious | None | None | None | None | N |
| A/Y | 0.7053 | likely_pathogenic | 0.7256 | pathogenic | -0.836 | Destabilizing | 0.998 | D | 0.88 | 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.