Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24542 | 73849;73850;73851 | chr2:178572508;178572507;178572506 | chr2:179437235;179437234;179437233 |
| N2AB | 22901 | 68926;68927;68928 | chr2:178572508;178572507;178572506 | chr2:179437235;179437234;179437233 |
| N2A | 21974 | 66145;66146;66147 | chr2:178572508;178572507;178572506 | chr2:179437235;179437234;179437233 |
| N2B | 15477 | 46654;46655;46656 | chr2:178572508;178572507;178572506 | chr2:179437235;179437234;179437233 |
| Novex-1 | 15602 | 47029;47030;47031 | chr2:178572508;178572507;178572506 | chr2:179437235;179437234;179437233 |
| Novex-2 | 15669 | 47230;47231;47232 | chr2:178572508;178572507;178572506 | chr2:179437235;179437234;179437233 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 0.991 | N | 0.691 | 0.453 | 0.566193126947 | gnomAD-4.0.0 | 6.84383E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99607E-07 | 0 | 0 |
| P/R | rs901760899  |
None | 0.991 | N | 0.715 | 0.456 | 0.587058026133 | gnomAD-4.0.0 | 3.42192E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59843E-06 | 0 | 1.65706E-05 |
| P/T | None | None | 0.805 | N | 0.601 | 0.334 | 0.479286488449 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0681 | likely_benign | 0.0617 | benign | -1.879 | Destabilizing | 0.035 | N | 0.339 | neutral | N | 0.492105851 | None | None | N |
| P/C | 0.4332 | ambiguous | 0.4148 | ambiguous | -1.233 | Destabilizing | 0.997 | D | 0.729 | prob.delet. | None | None | None | None | N |
| P/D | 0.8121 | likely_pathogenic | 0.7394 | pathogenic | -2.033 | Highly Destabilizing | 0.604 | D | 0.629 | neutral | None | None | None | None | N |
| P/E | 0.5429 | ambiguous | 0.464 | ambiguous | -1.932 | Destabilizing | 0.828 | D | 0.628 | neutral | None | None | None | None | N |
| P/F | 0.5244 | ambiguous | 0.4427 | ambiguous | -1.306 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| P/G | 0.4565 | ambiguous | 0.394 | ambiguous | -2.291 | Highly Destabilizing | 0.816 | D | 0.561 | neutral | None | None | None | None | N |
| P/H | 0.304 | likely_benign | 0.2641 | benign | -1.809 | Destabilizing | 0.998 | D | 0.702 | prob.neutral | None | None | None | None | N |
| P/I | 0.1949 | likely_benign | 0.1713 | benign | -0.792 | Destabilizing | 0.997 | D | 0.749 | deleterious | None | None | None | None | N |
| P/K | 0.5517 | ambiguous | 0.4815 | ambiguous | -1.675 | Destabilizing | 0.994 | D | 0.623 | neutral | None | None | None | None | N |
| P/L | 0.0964 | likely_benign | 0.0852 | benign | -0.792 | Destabilizing | 0.991 | D | 0.691 | prob.neutral | N | 0.5056361 | None | None | N |
| P/M | 0.1874 | likely_benign | 0.1812 | benign | -0.615 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| P/N | 0.4217 | ambiguous | 0.3926 | ambiguous | -1.636 | Destabilizing | 0.038 | N | 0.415 | neutral | None | None | None | None | N |
| P/Q | 0.2184 | likely_benign | 0.1981 | benign | -1.673 | Destabilizing | 0.977 | D | 0.677 | prob.neutral | N | 0.503256244 | None | None | N |
| P/R | 0.463 | ambiguous | 0.3709 | ambiguous | -1.236 | Destabilizing | 0.991 | D | 0.715 | prob.delet. | N | 0.494355474 | None | None | N |
| P/S | 0.1423 | likely_benign | 0.1201 | benign | -2.175 | Highly Destabilizing | 0.822 | D | 0.547 | neutral | N | 0.483239431 | None | None | N |
| P/T | 0.1047 | likely_benign | 0.0901 | benign | -1.946 | Destabilizing | 0.805 | D | 0.601 | neutral | N | 0.511965976 | None | None | N |
| P/V | 0.1363 | likely_benign | 0.1214 | benign | -1.123 | Destabilizing | 0.964 | D | 0.641 | neutral | None | None | None | None | N |
| P/W | 0.8634 | likely_pathogenic | 0.7972 | pathogenic | -1.612 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| P/Y | 0.578 | likely_pathogenic | 0.5074 | ambiguous | -1.298 | Destabilizing | 1.0 | D | 0.744 | 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.