Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4774 | 14545;14546;14547 | chr2:178738133;178738132;178738131 | chr2:179602860;179602859;179602858 |
| N2AB | 4457 | 13594;13595;13596 | chr2:178738133;178738132;178738131 | chr2:179602860;179602859;179602858 |
| N2A | 3530 | 10813;10814;10815 | chr2:178738133;178738132;178738131 | chr2:179602860;179602859;179602858 |
| N2B | 4411 | 13456;13457;13458 | chr2:178738133;178738132;178738131 | chr2:179602860;179602859;179602858 |
| Novex-1 | 4536 | 13831;13832;13833 | chr2:178738133;178738132;178738131 | chr2:179602860;179602859;179602858 |
| Novex-2 | 4603 | 14032;14033;14034 | chr2:178738133;178738132;178738131 | chr2:179602860;179602859;179602858 |
| 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/P | None | None | 0.996 | N | 0.857 | 0.67 | 0.525561869914 | gnomAD-4.0.0 | 2.05267E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79897E-06 | 0 | 1.65662E-05 |
| A/S | rs1404878972  |
-1.669 | 0.928 | N | 0.589 | 0.502 | 0.396645960531 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.88E-06 | 0 |
| A/S | rs1404878972 |
-1.669 | 0.928 | N | 0.589 | 0.502 | 0.396645960531 | gnomAD-4.0.0 | 5.4738E-06 | None | None | None | None | N | None | 2.98739E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39691E-06 | 1.15937E-05 | 0 |
| A/T | rs1404878972 |
None | 0.928 | N | 0.652 | 0.538 | 0.403896168776 | gnomAD-4.0.0 | 3.42112E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49742E-06 | 0 | 0 |
| A/V | rs879085292 |
None | 0.085 | N | 0.407 | 0.232 | None | gnomAD-4.0.0 | 4.10535E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.3969E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.881 | likely_pathogenic | 0.9357 | pathogenic | -1.593 | Destabilizing | 0.999 | D | 0.823 | deleterious | None | None | None | None | N |
| A/D | 0.9941 | likely_pathogenic | 0.9962 | pathogenic | -2.586 | Highly Destabilizing | 0.996 | D | 0.848 | deleterious | N | 0.511991537 | None | None | N |
| A/E | 0.9856 | likely_pathogenic | 0.9911 | pathogenic | -2.42 | Highly Destabilizing | 0.992 | D | 0.833 | deleterious | None | None | None | None | N |
| A/F | 0.862 | likely_pathogenic | 0.9302 | pathogenic | -0.846 | Destabilizing | 0.983 | D | 0.866 | deleterious | None | None | None | None | N |
| A/G | 0.4119 | ambiguous | 0.4501 | ambiguous | -1.734 | Destabilizing | 0.963 | D | 0.575 | neutral | N | 0.512147995 | None | None | N |
| A/H | 0.9944 | likely_pathogenic | 0.9968 | pathogenic | -1.983 | Destabilizing | 0.999 | D | 0.851 | deleterious | None | None | None | None | N |
| A/I | 0.5521 | ambiguous | 0.7978 | pathogenic | -0.105 | Destabilizing | 0.745 | D | 0.728 | prob.delet. | None | None | None | None | N |
| A/K | 0.997 | likely_pathogenic | 0.9982 | pathogenic | -1.372 | Destabilizing | 0.992 | D | 0.838 | deleterious | None | None | None | None | N |
| A/L | 0.5635 | ambiguous | 0.7327 | pathogenic | -0.105 | Destabilizing | 0.895 | D | 0.665 | neutral | None | None | None | None | N |
| A/M | 0.7497 | likely_pathogenic | 0.8858 | pathogenic | -0.452 | Destabilizing | 0.996 | D | 0.866 | deleterious | None | None | None | None | N |
| A/N | 0.9871 | likely_pathogenic | 0.9932 | pathogenic | -1.635 | Destabilizing | 0.997 | D | 0.851 | deleterious | None | None | None | None | N |
| A/P | 0.9847 | likely_pathogenic | 0.9912 | pathogenic | -0.457 | Destabilizing | 0.996 | D | 0.857 | deleterious | N | 0.512159048 | None | None | N |
| A/Q | 0.9835 | likely_pathogenic | 0.9894 | pathogenic | -1.516 | Destabilizing | 0.997 | D | 0.856 | deleterious | None | None | None | None | N |
| A/R | 0.9894 | likely_pathogenic | 0.9928 | pathogenic | -1.359 | Destabilizing | 0.992 | D | 0.852 | deleterious | None | None | None | None | N |
| A/S | 0.5181 | ambiguous | 0.6426 | pathogenic | -2.051 | Highly Destabilizing | 0.928 | D | 0.589 | neutral | N | 0.512057402 | None | None | N |
| A/T | 0.604 | likely_pathogenic | 0.7948 | pathogenic | -1.765 | Destabilizing | 0.928 | D | 0.652 | neutral | N | 0.512275025 | None | None | N |
| A/V | 0.279 | likely_benign | 0.5216 | ambiguous | -0.457 | Destabilizing | 0.085 | N | 0.407 | neutral | N | 0.502508322 | None | None | N |
| A/W | 0.9945 | likely_pathogenic | 0.9974 | pathogenic | -1.521 | Destabilizing | 0.999 | D | 0.841 | deleterious | None | None | None | None | N |
| A/Y | 0.968 | likely_pathogenic | 0.9819 | pathogenic | -1.035 | Destabilizing | 0.992 | D | 0.876 | 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.