Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
| N2AB | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
| N2A | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
| N2B | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
| Novex-1 | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
| Novex-2 | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
| Novex-3 | 133 | 622;623;624 | chr2:178800581;178800580;178800579 | chr2:179665308;179665307;179665306 |
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/A | rs556390708  |
None | 0.252 | D | 0.443 | 0.649 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.583(TCAP) | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/A | rs556390708 |
None | 0.252 | D | 0.443 | 0.649 | None | gnomAD-4.0.0 | 6.57082E-06 | None | None | None | -0.583(TCAP) | N | None | 2.41371E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | None | None | 0.999 | D | 0.747 | 0.652 | 0.875033115104 | gnomAD-4.0.0 | 1.59062E-06 | None | None | None | -0.94(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85662E-06 | 0 | 0 |
| P/S | rs556390708 |
-2.096 | 0.977 | D | 0.657 | 0.721 | 0.548443230319 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.664(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| P/S | rs556390708 |
-2.096 | 0.977 | D | 0.657 | 0.721 | 0.548443230319 | 1000 genomes | 1.99681E-04 | None | None | None | -0.664(TCAP) | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| P/S | rs556390708 |
-2.096 | 0.977 | D | 0.657 | 0.721 | 0.548443230319 | gnomAD-4.0.0 | 6.56573E-06 | None | None | None | -0.664(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| P/T | None | None | 0.543 | D | 0.447 | 0.722 | 0.582170006919 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | -0.838(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6894 | likely_pathogenic | 0.7603 | pathogenic | -1.851 | Destabilizing | 0.252 | N | 0.443 | neutral | D | 0.66267385 | None | -0.583(TCAP) | N |
| P/C | 0.9947 | likely_pathogenic | 0.9958 | pathogenic | -1.554 | Destabilizing | 1.0 | D | 0.748 | deleterious | None | None | None | -1.2(TCAP) | N |
| P/D | 0.9976 | likely_pathogenic | 0.9986 | pathogenic | -2.239 | Highly Destabilizing | 0.983 | D | 0.712 | prob.delet. | None | None | None | -1.348(TCAP) | N |
| P/E | 0.9939 | likely_pathogenic | 0.9964 | pathogenic | -2.151 | Highly Destabilizing | 0.989 | D | 0.721 | prob.delet. | None | None | None | -1.53(TCAP) | N |
| P/F | 0.9986 | likely_pathogenic | 0.9991 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | -0.458(TCAP) | N |
| P/G | 0.983 | likely_pathogenic | 0.9893 | pathogenic | -2.249 | Highly Destabilizing | 0.988 | D | 0.672 | neutral | None | None | None | -0.486(TCAP) | N |
| P/H | 0.9943 | likely_pathogenic | 0.9964 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | D | 0.804659281 | None | -0.366(TCAP) | N |
| P/I | 0.9822 | likely_pathogenic | 0.9874 | pathogenic | -0.807 | Destabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | -0.94(TCAP) | N |
| P/K | 0.9975 | likely_pathogenic | 0.9984 | pathogenic | -1.44 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | -1.581(TCAP) | N |
| P/L | 0.9385 | likely_pathogenic | 0.9606 | pathogenic | -0.807 | Destabilizing | 0.999 | D | 0.747 | deleterious | D | 0.740734466 | None | -0.94(TCAP) | N |
| P/M | 0.9907 | likely_pathogenic | 0.9941 | pathogenic | -0.846 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | -1.01(TCAP) | N |
| P/N | 0.9963 | likely_pathogenic | 0.9978 | pathogenic | -1.478 | Destabilizing | 0.994 | D | 0.749 | deleterious | None | None | None | -0.995(TCAP) | N |
| P/Q | 0.9901 | likely_pathogenic | 0.9941 | pathogenic | -1.557 | Destabilizing | 0.999 | D | 0.722 | prob.delet. | None | None | None | -1.104(TCAP) | N |
| P/R | 0.992 | likely_pathogenic | 0.9946 | pathogenic | -1.079 | Destabilizing | 1.0 | D | 0.741 | deleterious | D | 0.80385033 | None | -1.631(TCAP) | N |
| P/S | 0.953 | likely_pathogenic | 0.9713 | pathogenic | -2.039 | Highly Destabilizing | 0.977 | D | 0.657 | neutral | D | 0.767729633 | None | -0.664(TCAP) | N |
| P/T | 0.9363 | likely_pathogenic | 0.9578 | pathogenic | -1.833 | Destabilizing | 0.543 | D | 0.447 | neutral | D | 0.782733684 | None | -0.838(TCAP) | N |
| P/V | 0.942 | likely_pathogenic | 0.9579 | pathogenic | -1.124 | Destabilizing | 0.973 | D | 0.681 | prob.neutral | None | None | None | -0.812(TCAP) | N |
| P/W | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -1.659 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | -0.648(TCAP) | N |
| P/Y | 0.9988 | likely_pathogenic | 0.9992 | pathogenic | -1.318 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | -0.472(TCAP) | 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.