Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18787 | 56584;56585;56586 | chr2:178599434;178599433;178599432 | chr2:179464161;179464160;179464159 |
| N2AB | 17146 | 51661;51662;51663 | chr2:178599434;178599433;178599432 | chr2:179464161;179464160;179464159 |
| N2A | 16219 | 48880;48881;48882 | chr2:178599434;178599433;178599432 | chr2:179464161;179464160;179464159 |
| N2B | 9722 | 29389;29390;29391 | chr2:178599434;178599433;178599432 | chr2:179464161;179464160;179464159 |
| Novex-1 | 9847 | 29764;29765;29766 | chr2:178599434;178599433;178599432 | chr2:179464161;179464160;179464159 |
| Novex-2 | 9914 | 29965;29966;29967 | chr2:178599434;178599433;178599432 | chr2:179464161;179464160;179464159 |
| 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 | 0.995 | N | 0.905 | 0.409 | 0.631724915229 | gnomAD-4.0.0 | 7.24553E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.30271E-07 | 0 | 0 |
| P/R | rs1227865413  |
-0.946 | 1.0 | N | 0.941 | 0.491 | 0.512595481341 | gnomAD-2.1.1 | 5.38E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.11E-05 | 0 |
| P/R | rs1227865413 |
-0.946 | 1.0 | N | 0.941 | 0.491 | 0.512595481341 | gnomAD-4.0.0 | 2.17366E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.79081E-06 | 0 | 0 |
| P/S | None | None | 0.999 | N | 0.922 | 0.32 | 0.331365685468 | gnomAD-4.0.0 | 1.82357E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.85957E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1213 | likely_benign | 0.098 | benign | -1.755 | Destabilizing | 0.992 | D | 0.817 | deleterious | N | 0.465321894 | None | None | N |
| P/C | 0.5379 | ambiguous | 0.4737 | ambiguous | -1.12 | Destabilizing | 1.0 | D | 0.91 | deleterious | None | None | None | None | N |
| P/D | 0.8128 | likely_pathogenic | 0.7134 | pathogenic | -2.019 | Highly Destabilizing | 1.0 | D | 0.922 | deleterious | None | None | None | None | N |
| P/E | 0.4875 | ambiguous | 0.3781 | ambiguous | -1.996 | Destabilizing | 1.0 | D | 0.933 | deleterious | None | None | None | None | N |
| P/F | 0.5902 | likely_pathogenic | 0.5106 | ambiguous | -1.262 | Destabilizing | 1.0 | D | 0.934 | deleterious | None | None | None | None | N |
| P/G | 0.6269 | likely_pathogenic | 0.5101 | ambiguous | -2.094 | Highly Destabilizing | 1.0 | D | 0.918 | deleterious | None | None | None | None | N |
| P/H | 0.3792 | ambiguous | 0.2835 | benign | -1.686 | Destabilizing | 1.0 | D | 0.906 | deleterious | N | 0.490148284 | None | None | N |
| P/I | 0.2616 | likely_benign | 0.2221 | benign | -0.895 | Destabilizing | 0.996 | D | 0.913 | deleterious | None | None | None | None | N |
| P/K | 0.3817 | ambiguous | 0.264 | benign | -1.517 | Destabilizing | 1.0 | D | 0.931 | deleterious | None | None | None | None | N |
| P/L | 0.1743 | likely_benign | 0.1405 | benign | -0.895 | Destabilizing | 0.995 | D | 0.905 | deleterious | N | 0.488373857 | None | None | N |
| P/M | 0.3434 | ambiguous | 0.2823 | benign | -0.687 | Destabilizing | 1.0 | D | 0.928 | deleterious | None | None | None | None | N |
| P/N | 0.6515 | likely_pathogenic | 0.5448 | ambiguous | -1.323 | Destabilizing | 1.0 | D | 0.937 | deleterious | None | None | None | None | N |
| P/Q | 0.262 | likely_benign | 0.1915 | benign | -1.493 | Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| P/R | 0.2913 | likely_benign | 0.1976 | benign | -0.978 | Destabilizing | 1.0 | D | 0.941 | deleterious | N | 0.500490631 | None | None | N |
| P/S | 0.2778 | likely_benign | 0.2052 | benign | -1.793 | Destabilizing | 0.999 | D | 0.922 | deleterious | N | 0.473767732 | None | None | N |
| P/T | 0.2278 | likely_benign | 0.1653 | benign | -1.676 | Destabilizing | 0.998 | D | 0.919 | deleterious | N | 0.477524531 | None | None | N |
| P/V | 0.214 | likely_benign | 0.1712 | benign | -1.15 | Destabilizing | 0.833 | D | 0.678 | prob.neutral | None | None | None | None | N |
| P/W | 0.8271 | likely_pathogenic | 0.7568 | pathogenic | -1.516 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| P/Y | 0.624 | likely_pathogenic | 0.5286 | ambiguous | -1.258 | Destabilizing | 1.0 | D | 0.931 | 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.