Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14977 | 45154;45155;45156 | chr2:178621993;178621992;178621991 | chr2:179486720;179486719;179486718 |
| N2AB | 13336 | 40231;40232;40233 | chr2:178621993;178621992;178621991 | chr2:179486720;179486719;179486718 |
| N2A | 12409 | 37450;37451;37452 | chr2:178621993;178621992;178621991 | chr2:179486720;179486719;179486718 |
| N2B | 5912 | 17959;17960;17961 | chr2:178621993;178621992;178621991 | chr2:179486720;179486719;179486718 |
| Novex-1 | 6037 | 18334;18335;18336 | chr2:178621993;178621992;178621991 | chr2:179486720;179486719;179486718 |
| Novex-2 | 6104 | 18535;18536;18537 | chr2:178621993;178621992;178621991 | chr2:179486720;179486719;179486718 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs778989426  |
0.318 | 0.996 | N | 0.595 | 0.341 | 0.322230723748 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| D/N | rs778989426 |
0.318 | 0.996 | N | 0.595 | 0.341 | 0.322230723748 | gnomAD-4.0.0 | 6.58345E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| D/V | rs1343831802 |
0.228 | 0.085 | D | 0.483 | 0.432 | 0.416328079214 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.78E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.4387 | ambiguous | 0.5664 | pathogenic | -0.411 | Destabilizing | 0.865 | D | 0.593 | neutral | D | 0.6783693159999999 | None | None | N |
| D/C | 0.8582 | likely_pathogenic | 0.916 | pathogenic | -0.111 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| D/E | 0.4031 | ambiguous | 0.5197 | ambiguous | -0.354 | Destabilizing | 0.963 | D | 0.421 | neutral | N | 0.486615858 | None | None | N |
| D/F | 0.8793 | likely_pathogenic | 0.9288 | pathogenic | -0.144 | Destabilizing | 0.983 | D | 0.685 | prob.neutral | None | None | None | None | N |
| D/G | 0.2424 | likely_benign | 0.3418 | ambiguous | -0.653 | Destabilizing | 0.963 | D | 0.633 | neutral | N | 0.457200381 | None | None | N |
| D/H | 0.6679 | likely_pathogenic | 0.7789 | pathogenic | -0.009 | Destabilizing | 0.999 | D | 0.613 | neutral | D | 0.680069876 | None | None | N |
| D/I | 0.873 | likely_pathogenic | 0.9304 | pathogenic | 0.192 | Stabilizing | 0.911 | D | 0.671 | neutral | None | None | None | None | N |
| D/K | 0.7629 | likely_pathogenic | 0.8635 | pathogenic | 0.181 | Stabilizing | 0.992 | D | 0.67 | neutral | None | None | None | None | N |
| D/L | 0.7935 | likely_pathogenic | 0.8652 | pathogenic | 0.192 | Stabilizing | 0.968 | D | 0.649 | neutral | None | None | None | None | N |
| D/M | 0.9192 | likely_pathogenic | 0.9543 | pathogenic | 0.33 | Stabilizing | 0.996 | D | 0.647 | neutral | None | None | None | None | N |
| D/N | 0.1615 | likely_benign | 0.2354 | benign | -0.243 | Destabilizing | 0.996 | D | 0.595 | neutral | N | 0.445315147 | None | None | N |
| D/P | 0.9829 | likely_pathogenic | 0.9898 | pathogenic | 0.014 | Stabilizing | 0.997 | D | 0.647 | neutral | None | None | None | None | N |
| D/Q | 0.7011 | likely_pathogenic | 0.8185 | pathogenic | -0.174 | Destabilizing | 0.997 | D | 0.623 | neutral | None | None | None | None | N |
| D/R | 0.7365 | likely_pathogenic | 0.8294 | pathogenic | 0.423 | Stabilizing | 0.992 | D | 0.65 | neutral | None | None | None | None | N |
| D/S | 0.3036 | likely_benign | 0.4258 | ambiguous | -0.368 | Destabilizing | 0.983 | D | 0.598 | neutral | None | None | None | None | N |
| D/T | 0.7399 | likely_pathogenic | 0.8396 | pathogenic | -0.17 | Destabilizing | 0.983 | D | 0.633 | neutral | None | None | None | None | N |
| D/V | 0.6812 | likely_pathogenic | 0.7891 | pathogenic | 0.014 | Stabilizing | 0.085 | N | 0.483 | neutral | D | 0.61918124 | None | None | N |
| D/W | 0.959 | likely_pathogenic | 0.9727 | pathogenic | 0.061 | Stabilizing | 0.999 | D | 0.657 | neutral | None | None | None | None | N |
| D/Y | 0.4337 | ambiguous | 0.5502 | ambiguous | 0.114 | Stabilizing | 0.997 | D | 0.669 | neutral | D | 0.68018966 | 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.