Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31726 | 95401;95402;95403 | chr2:178546060;178546059;178546058 | chr2:179410787;179410786;179410785 |
| N2AB | 30085 | 90478;90479;90480 | chr2:178546060;178546059;178546058 | chr2:179410787;179410786;179410785 |
| N2A | 29158 | 87697;87698;87699 | chr2:178546060;178546059;178546058 | chr2:179410787;179410786;179410785 |
| N2B | 22661 | 68206;68207;68208 | chr2:178546060;178546059;178546058 | chr2:179410787;179410786;179410785 |
| Novex-1 | 22786 | 68581;68582;68583 | chr2:178546060;178546059;178546058 | chr2:179410787;179410786;179410785 |
| Novex-2 | 22853 | 68782;68783;68784 | chr2:178546060;178546059;178546058 | chr2:179410787;179410786;179410785 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs761422470  |
-1.068 | 0.998 | D | 0.473 | 0.502 | 0.225215365344 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66058E-04 |
| T/A | rs761422470 |
-1.068 | 0.998 | D | 0.473 | 0.502 | 0.225215365344 | gnomAD-4.0.0 | 2.73723E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.47222E-04 | 1.79914E-06 | 0 | 0 |
| T/S | None | None | 0.996 | N | 0.479 | 0.401 | 0.199424873507 | gnomAD-4.0.0 | 1.36861E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79914E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1857 | likely_benign | 0.1998 | benign | -0.934 | Destabilizing | 0.998 | D | 0.473 | neutral | D | 0.524562199 | None | None | N |
| T/C | 0.5404 | ambiguous | 0.555 | ambiguous | -0.714 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| T/D | 0.7947 | likely_pathogenic | 0.848 | pathogenic | -0.664 | Destabilizing | 0.998 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/E | 0.7103 | likely_pathogenic | 0.7592 | pathogenic | -0.612 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/F | 0.326 | likely_benign | 0.374 | ambiguous | -0.828 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| T/G | 0.5057 | ambiguous | 0.5364 | ambiguous | -1.241 | Destabilizing | 0.997 | D | 0.654 | neutral | None | None | None | None | N |
| T/H | 0.3998 | ambiguous | 0.4441 | ambiguous | -1.495 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| T/I | 0.2572 | likely_benign | 0.2879 | benign | -0.189 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.485918322 | None | None | N |
| T/K | 0.5855 | likely_pathogenic | 0.6512 | pathogenic | -0.807 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/L | 0.1579 | likely_benign | 0.1712 | benign | -0.189 | Destabilizing | 0.998 | D | 0.612 | neutral | None | None | None | None | N |
| T/M | 0.144 | likely_benign | 0.1486 | benign | 0.043 | Stabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| T/N | 0.2572 | likely_benign | 0.2744 | benign | -0.92 | Destabilizing | 0.884 | D | 0.363 | neutral | N | 0.518809663 | None | None | N |
| T/P | 0.5934 | likely_pathogenic | 0.6767 | pathogenic | -0.405 | Destabilizing | 1.0 | D | 0.759 | deleterious | N | 0.515734504 | None | None | N |
| T/Q | 0.4736 | ambiguous | 0.5091 | ambiguous | -1.037 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| T/R | 0.4985 | ambiguous | 0.5695 | pathogenic | -0.655 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| T/S | 0.1738 | likely_benign | 0.186 | benign | -1.197 | Destabilizing | 0.996 | D | 0.479 | neutral | N | 0.4932765 | None | None | N |
| T/V | 0.1876 | likely_benign | 0.2041 | benign | -0.405 | Destabilizing | 1.0 | D | 0.505 | neutral | None | None | None | None | N |
| T/W | 0.7483 | likely_pathogenic | 0.7893 | pathogenic | -0.777 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| T/Y | 0.4028 | ambiguous | 0.4282 | ambiguous | -0.524 | Destabilizing | 1.0 | D | 0.844 | 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.