Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28092 | 84499;84500;84501 | chr2:178561858;178561857;178561856 | chr2:179426585;179426584;179426583 |
| N2AB | 26451 | 79576;79577;79578 | chr2:178561858;178561857;178561856 | chr2:179426585;179426584;179426583 |
| N2A | 25524 | 76795;76796;76797 | chr2:178561858;178561857;178561856 | chr2:179426585;179426584;179426583 |
| N2B | 19027 | 57304;57305;57306 | chr2:178561858;178561857;178561856 | chr2:179426585;179426584;179426583 |
| Novex-1 | 19152 | 57679;57680;57681 | chr2:178561858;178561857;178561856 | chr2:179426585;179426584;179426583 |
| Novex-2 | 19219 | 57880;57881;57882 | chr2:178561858;178561857;178561856 | chr2:179426585;179426584;179426583 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | None | None | 0.998 | D | 0.893 | 0.609 | 0.87026763106 | gnomAD-4.0.0 | 6.8428E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65678E-05 |
| V/G | rs761184333  |
-3.334 | 0.994 | D | 0.897 | 0.594 | 0.850823999335 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/G | rs761184333 |
-3.334 | 0.994 | D | 0.897 | 0.594 | 0.850823999335 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/G | rs761184333 |
-3.334 | 0.994 | D | 0.897 | 0.594 | 0.850823999335 | gnomAD-4.0.0 | 3.09873E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.3905E-06 | 0 | 1.60123E-05 |
| V/I | None | None | 0.825 | N | 0.539 | 0.175 | 0.468168183122 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43291E-05 | 0 |
| V/L | None | None | 0.067 | N | 0.297 | 0.171 | 0.342168650903 | gnomAD-4.0.0 | 1.59168E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8585E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8292 | likely_pathogenic | 0.7576 | pathogenic | -2.27 | Highly Destabilizing | 0.958 | D | 0.604 | neutral | D | 0.549212714 | None | None | N |
| V/C | 0.9822 | likely_pathogenic | 0.9689 | pathogenic | -1.534 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| V/D | 0.9992 | likely_pathogenic | 0.9984 | pathogenic | -3.204 | Highly Destabilizing | 0.998 | D | 0.893 | deleterious | D | 0.568077438 | None | None | N |
| V/E | 0.9966 | likely_pathogenic | 0.9941 | pathogenic | -2.859 | Highly Destabilizing | 0.995 | D | 0.883 | deleterious | None | None | None | None | N |
| V/F | 0.9388 | likely_pathogenic | 0.8859 | pathogenic | -1.312 | Destabilizing | 0.988 | D | 0.819 | deleterious | D | 0.567823948 | None | None | N |
| V/G | 0.971 | likely_pathogenic | 0.9504 | pathogenic | -2.906 | Highly Destabilizing | 0.994 | D | 0.897 | deleterious | D | 0.568077438 | None | None | N |
| V/H | 0.9991 | likely_pathogenic | 0.9981 | pathogenic | -2.876 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| V/I | 0.107 | likely_benign | 0.1027 | benign | -0.407 | Destabilizing | 0.825 | D | 0.539 | neutral | N | 0.476080393 | None | None | N |
| V/K | 0.9974 | likely_pathogenic | 0.9955 | pathogenic | -1.85 | Destabilizing | 0.995 | D | 0.883 | deleterious | None | None | None | None | N |
| V/L | 0.5972 | likely_pathogenic | 0.5367 | ambiguous | -0.407 | Destabilizing | 0.067 | N | 0.297 | neutral | N | 0.517951232 | None | None | N |
| V/M | 0.8064 | likely_pathogenic | 0.7023 | pathogenic | -0.6 | Destabilizing | 0.991 | D | 0.707 | prob.neutral | None | None | None | None | N |
| V/N | 0.998 | likely_pathogenic | 0.9961 | pathogenic | -2.638 | Highly Destabilizing | 0.998 | D | 0.895 | deleterious | None | None | None | None | N |
| V/P | 0.9964 | likely_pathogenic | 0.995 | pathogenic | -1.01 | Destabilizing | 0.998 | D | 0.879 | deleterious | None | None | None | None | N |
| V/Q | 0.996 | likely_pathogenic | 0.9925 | pathogenic | -2.203 | Highly Destabilizing | 0.998 | D | 0.893 | deleterious | None | None | None | None | N |
| V/R | 0.993 | likely_pathogenic | 0.9886 | pathogenic | -2.093 | Highly Destabilizing | 0.995 | D | 0.897 | deleterious | None | None | None | None | N |
| V/S | 0.9822 | likely_pathogenic | 0.9674 | pathogenic | -3.118 | Highly Destabilizing | 0.995 | D | 0.876 | deleterious | None | None | None | None | N |
| V/T | 0.8885 | likely_pathogenic | 0.8357 | pathogenic | -2.598 | Highly Destabilizing | 0.968 | D | 0.636 | neutral | None | None | None | None | N |
| V/W | 0.9991 | likely_pathogenic | 0.9979 | pathogenic | -1.85 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | N |
| V/Y | 0.9966 | likely_pathogenic | 0.9928 | pathogenic | -1.523 | Destabilizing | 0.995 | D | 0.815 | 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.