Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27736 | 83431;83432;83433 | chr2:178562926;178562925;178562924 | chr2:179427653;179427652;179427651 |
| N2AB | 26095 | 78508;78509;78510 | chr2:178562926;178562925;178562924 | chr2:179427653;179427652;179427651 |
| N2A | 25168 | 75727;75728;75729 | chr2:178562926;178562925;178562924 | chr2:179427653;179427652;179427651 |
| N2B | 18671 | 56236;56237;56238 | chr2:178562926;178562925;178562924 | chr2:179427653;179427652;179427651 |
| Novex-1 | 18796 | 56611;56612;56613 | chr2:178562926;178562925;178562924 | chr2:179427653;179427652;179427651 |
| Novex-2 | 18863 | 56812;56813;56814 | chr2:178562926;178562925;178562924 | chr2:179427653;179427652;179427651 |
| 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/A | rs1370518448  |
None | 0.63 | N | 0.526 | 0.362 | 0.698509492642 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs1370518448 |
None | 0.63 | N | 0.526 | 0.362 | 0.698509492642 | gnomAD-4.0.0 | 2.56282E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.09065E-05 | 0 | None | 0 | 0 | 2.39335E-06 | 0 | 0 |
| V/F | rs373638788 |
-1.609 | 0.983 | D | 0.72 | 0.691 | 0.839994840878 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| V/F | rs373638788 |
-1.609 | 0.983 | D | 0.72 | 0.691 | 0.839994840878 | gnomAD-4.0.0 | 2.73718E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59801E-06 | 0 | 0 |
| V/I | rs373638788 |
-0.849 | 0.873 | N | 0.53 | 0.362 | 0.614010665196 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| V/I | rs373638788 |
-0.849 | 0.873 | N | 0.53 | 0.362 | 0.614010665196 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs373638788 |
-0.849 | 0.873 | N | 0.53 | 0.362 | 0.614010665196 | gnomAD-4.0.0 | 6.19775E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47634E-06 | 0 | 0 |
| V/L | None | None | 0.773 | N | 0.537 | 0.479 | 0.727553539088 | gnomAD-4.0.0 | 1.36859E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31873E-05 | 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 | 0.5539 | ambiguous | 0.5646 | pathogenic | -1.834 | Destabilizing | 0.63 | D | 0.526 | neutral | N | 0.500005763 | None | None | N |
| V/C | 0.8833 | likely_pathogenic | 0.8862 | pathogenic | -2.369 | Highly Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| V/D | 0.9937 | likely_pathogenic | 0.9944 | pathogenic | -3.245 | Highly Destabilizing | 0.967 | D | 0.739 | prob.delet. | D | 0.556007706 | None | None | N |
| V/E | 0.9885 | likely_pathogenic | 0.9899 | pathogenic | -3.157 | Highly Destabilizing | 0.975 | D | 0.693 | prob.neutral | None | None | None | None | N |
| V/F | 0.9612 | likely_pathogenic | 0.9675 | pathogenic | -1.401 | Destabilizing | 0.983 | D | 0.72 | prob.delet. | D | 0.543890932 | None | None | N |
| V/G | 0.8601 | likely_pathogenic | 0.8732 | pathogenic | -2.189 | Highly Destabilizing | 0.805 | D | 0.689 | prob.neutral | D | 0.544397911 | None | None | N |
| V/H | 0.9968 | likely_pathogenic | 0.9971 | pathogenic | -1.606 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| V/I | 0.1776 | likely_benign | 0.1969 | benign | -0.9 | Destabilizing | 0.873 | D | 0.53 | neutral | N | 0.493369466 | None | None | N |
| V/K | 0.9926 | likely_pathogenic | 0.9934 | pathogenic | -1.728 | Destabilizing | 0.975 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/L | 0.7962 | likely_pathogenic | 0.8254 | pathogenic | -0.9 | Destabilizing | 0.773 | D | 0.537 | neutral | N | 0.506135031 | None | None | N |
| V/M | 0.7137 | likely_pathogenic | 0.7704 | pathogenic | -1.223 | Destabilizing | 0.996 | D | 0.671 | neutral | None | None | None | None | N |
| V/N | 0.9652 | likely_pathogenic | 0.9699 | pathogenic | -2.046 | Highly Destabilizing | 0.975 | D | 0.748 | deleterious | None | None | None | None | N |
| V/P | 0.9807 | likely_pathogenic | 0.9826 | pathogenic | -1.184 | Destabilizing | 0.987 | D | 0.717 | prob.delet. | None | None | None | None | N |
| V/Q | 0.9858 | likely_pathogenic | 0.9877 | pathogenic | -2.176 | Highly Destabilizing | 0.975 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/R | 0.9888 | likely_pathogenic | 0.989 | pathogenic | -1.255 | Destabilizing | 0.975 | D | 0.748 | deleterious | None | None | None | None | N |
| V/S | 0.7862 | likely_pathogenic | 0.8029 | pathogenic | -2.487 | Highly Destabilizing | 0.253 | N | 0.471 | neutral | None | None | None | None | N |
| V/T | 0.5922 | likely_pathogenic | 0.6161 | pathogenic | -2.286 | Highly Destabilizing | 0.845 | D | 0.547 | neutral | None | None | None | None | N |
| V/W | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.7 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/Y | 0.996 | likely_pathogenic | 0.9965 | pathogenic | -1.367 | Destabilizing | 0.996 | D | 0.721 | prob.delet. | 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.