Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23178 | 69757;69758;69759 | chr2:178576712;178576711;178576710 | chr2:179441439;179441438;179441437 |
| N2AB | 21537 | 64834;64835;64836 | chr2:178576712;178576711;178576710 | chr2:179441439;179441438;179441437 |
| N2A | 20610 | 62053;62054;62055 | chr2:178576712;178576711;178576710 | chr2:179441439;179441438;179441437 |
| N2B | 14113 | 42562;42563;42564 | chr2:178576712;178576711;178576710 | chr2:179441439;179441438;179441437 |
| Novex-1 | 14238 | 42937;42938;42939 | chr2:178576712;178576711;178576710 | chr2:179441439;179441438;179441437 |
| Novex-2 | 14305 | 43138;43139;43140 | chr2:178576712;178576711;178576710 | chr2:179441439;179441438;179441437 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/M | rs376978126  |
-1.792 | 0.999 | N | 0.737 | 0.334 | None | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.69E-05 | 0 |
| R/M | rs376978126 |
-1.792 | 0.999 | N | 0.737 | 0.334 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17709E-04 | 0 | 0 |
| R/M | rs376978126 |
-1.792 | 0.999 | N | 0.737 | 0.334 | None | gnomAD-4.0.0 | 2.23133E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.96708E-05 | 0 | 1.60138E-05 |
| R/S | None | None | 0.892 | N | 0.713 | 0.315 | 0.28297238246 | gnomAD-4.0.0 | 6.84274E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99565E-07 | 0 | 0 |
| R/T | None | None | 0.967 | N | 0.723 | 0.289 | 0.371531589858 | gnomAD-4.0.0 | 6.84276E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99567E-07 | 0 | 0 |
| R/W | None | None | 0.999 | N | 0.735 | 0.271 | 0.463928626847 | gnomAD-4.0.0 | 1.59161E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41313E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9368 | likely_pathogenic | 0.9431 | pathogenic | -2.103 | Highly Destabilizing | 0.845 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/C | 0.3864 | ambiguous | 0.3996 | ambiguous | -2.077 | Highly Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | N |
| R/D | 0.993 | likely_pathogenic | 0.9943 | pathogenic | -1.509 | Destabilizing | 0.975 | D | 0.756 | deleterious | None | None | None | None | N |
| R/E | 0.919 | likely_pathogenic | 0.9332 | pathogenic | -1.251 | Destabilizing | 0.845 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/F | 0.8745 | likely_pathogenic | 0.8629 | pathogenic | -1.17 | Destabilizing | 0.996 | D | 0.819 | deleterious | None | None | None | None | N |
| R/G | 0.8871 | likely_pathogenic | 0.9052 | pathogenic | -2.48 | Highly Destabilizing | 0.892 | D | 0.755 | deleterious | N | 0.470456959 | None | None | N |
| R/H | 0.3272 | likely_benign | 0.3279 | benign | -1.764 | Destabilizing | 0.987 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/I | 0.7004 | likely_pathogenic | 0.6962 | pathogenic | -0.987 | Destabilizing | 0.987 | D | 0.815 | deleterious | None | None | None | None | N |
| R/K | 0.1511 | likely_benign | 0.1452 | benign | -1.16 | Destabilizing | 0.025 | N | 0.397 | neutral | N | 0.430379815 | None | None | N |
| R/L | 0.6182 | likely_pathogenic | 0.6036 | pathogenic | -0.987 | Destabilizing | 0.916 | D | 0.755 | deleterious | None | None | None | None | N |
| R/M | 0.6316 | likely_pathogenic | 0.6385 | pathogenic | -1.482 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | N | 0.500567832 | None | None | N |
| R/N | 0.975 | likely_pathogenic | 0.979 | pathogenic | -1.801 | Destabilizing | 0.975 | D | 0.692 | prob.neutral | None | None | None | None | N |
| R/P | 0.9958 | likely_pathogenic | 0.9966 | pathogenic | -1.351 | Destabilizing | 0.987 | D | 0.768 | deleterious | None | None | None | None | N |
| R/Q | 0.2901 | likely_benign | 0.3044 | benign | -1.577 | Destabilizing | 0.975 | D | 0.696 | prob.neutral | None | None | None | None | N |
| R/S | 0.9649 | likely_pathogenic | 0.9703 | pathogenic | -2.643 | Highly Destabilizing | 0.892 | D | 0.713 | prob.delet. | N | 0.473241662 | None | None | N |
| R/T | 0.8821 | likely_pathogenic | 0.9017 | pathogenic | -2.146 | Highly Destabilizing | 0.967 | D | 0.723 | prob.delet. | N | 0.469443 | None | None | N |
| R/V | 0.7715 | likely_pathogenic | 0.7708 | pathogenic | -1.351 | Destabilizing | 0.975 | D | 0.795 | deleterious | None | None | None | None | N |
| R/W | 0.4517 | ambiguous | 0.4531 | ambiguous | -0.643 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | N | 0.513283626 | None | None | N |
| R/Y | 0.719 | likely_pathogenic | 0.6886 | pathogenic | -0.582 | Destabilizing | 0.996 | D | 0.795 | 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.