Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19672 | 59239;59240;59241 | chr2:178593194;178593193;178593192 | chr2:179457921;179457920;179457919 |
| N2AB | 18031 | 54316;54317;54318 | chr2:178593194;178593193;178593192 | chr2:179457921;179457920;179457919 |
| N2A | 17104 | 51535;51536;51537 | chr2:178593194;178593193;178593192 | chr2:179457921;179457920;179457919 |
| N2B | 10607 | 32044;32045;32046 | chr2:178593194;178593193;178593192 | chr2:179457921;179457920;179457919 |
| Novex-1 | 10732 | 32419;32420;32421 | chr2:178593194;178593193;178593192 | chr2:179457921;179457920;179457919 |
| Novex-2 | 10799 | 32620;32621;32622 | chr2:178593194;178593193;178593192 | chr2:179457921;179457920;179457919 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1263299073  |
-1.534 | 0.025 | N | 0.46 | 0.204 | 0.356281029322 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs1263299073 |
-1.534 | 0.025 | N | 0.46 | 0.204 | 0.356281029322 | gnomAD-4.0.0 | 1.59233E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.7818E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/D | None | None | 0.303 | N | 0.703 | 0.441 | 0.627346566048 | gnomAD-4.0.0 | 1.59233E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43377E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2907 | likely_benign | 0.2782 | benign | -1.446 | Destabilizing | 0.025 | N | 0.46 | neutral | N | 0.507589804 | None | None | N |
| V/C | 0.6472 | likely_pathogenic | 0.6152 | pathogenic | -0.79 | Destabilizing | 0.869 | D | 0.512 | neutral | None | None | None | None | N |
| V/D | 0.7759 | likely_pathogenic | 0.7654 | pathogenic | -1.547 | Destabilizing | 0.303 | N | 0.703 | prob.delet. | N | 0.497310626 | None | None | N |
| V/E | 0.6244 | likely_pathogenic | 0.6323 | pathogenic | -1.385 | Destabilizing | 0.366 | N | 0.634 | neutral | None | None | None | None | N |
| V/F | 0.2275 | likely_benign | 0.1698 | benign | -0.791 | Destabilizing | None | N | 0.263 | neutral | N | 0.488524041 | None | None | N |
| V/G | 0.4571 | ambiguous | 0.45 | ambiguous | -1.911 | Destabilizing | 0.303 | N | 0.677 | prob.neutral | N | 0.497057136 | None | None | N |
| V/H | 0.7582 | likely_pathogenic | 0.7391 | pathogenic | -1.517 | Destabilizing | 0.869 | D | 0.677 | prob.neutral | None | None | None | None | N |
| V/I | 0.0788 | likely_benign | 0.0741 | benign | -0.197 | Destabilizing | None | N | 0.169 | neutral | N | 0.405732086 | None | None | N |
| V/K | 0.6717 | likely_pathogenic | 0.6925 | pathogenic | -1.145 | Destabilizing | 0.366 | N | 0.628 | neutral | None | None | None | None | N |
| V/L | 0.254 | likely_benign | 0.2238 | benign | -0.197 | Destabilizing | 0.002 | N | 0.373 | neutral | N | 0.50602958 | None | None | N |
| V/M | 0.2081 | likely_benign | 0.1839 | benign | -0.146 | Destabilizing | 0.221 | N | 0.479 | neutral | None | None | None | None | N |
| V/N | 0.5993 | likely_pathogenic | 0.5813 | pathogenic | -1.295 | Destabilizing | 0.637 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/P | 0.9529 | likely_pathogenic | 0.9382 | pathogenic | -0.582 | Destabilizing | 0.637 | D | 0.629 | neutral | None | None | None | None | N |
| V/Q | 0.5623 | ambiguous | 0.5839 | pathogenic | -1.214 | Destabilizing | 0.637 | D | 0.627 | neutral | None | None | None | None | N |
| V/R | 0.5944 | likely_pathogenic | 0.6054 | pathogenic | -0.936 | Destabilizing | 0.366 | N | 0.677 | prob.neutral | None | None | None | None | N |
| V/S | 0.4241 | ambiguous | 0.4132 | ambiguous | -1.896 | Destabilizing | 0.366 | N | 0.627 | neutral | None | None | None | None | N |
| V/T | 0.2664 | likely_benign | 0.2738 | benign | -1.598 | Destabilizing | 0.075 | N | 0.472 | neutral | None | None | None | None | N |
| V/W | 0.8888 | likely_pathogenic | 0.852 | pathogenic | -1.227 | Destabilizing | 0.869 | D | 0.721 | deleterious | None | None | None | None | N |
| V/Y | 0.6194 | likely_pathogenic | 0.5558 | ambiguous | -0.791 | Destabilizing | 0.125 | N | 0.529 | 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.