Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18299 | 55120;55121;55122 | chr2:178602507;178602506;178602505 | chr2:179467234;179467233;179467232 |
| N2AB | 16658 | 50197;50198;50199 | chr2:178602507;178602506;178602505 | chr2:179467234;179467233;179467232 |
| N2A | 15731 | 47416;47417;47418 | chr2:178602507;178602506;178602505 | chr2:179467234;179467233;179467232 |
| N2B | 9234 | 27925;27926;27927 | chr2:178602507;178602506;178602505 | chr2:179467234;179467233;179467232 |
| Novex-1 | 9359 | 28300;28301;28302 | chr2:178602507;178602506;178602505 | chr2:179467234;179467233;179467232 |
| Novex-2 | 9426 | 28501;28502;28503 | chr2:178602507;178602506;178602505 | chr2:179467234;179467233;179467232 |
| 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 | None | None | 1.0 | N | 0.68 | 0.339 | 0.428630128466 | gnomAD-4.0.0 | 6.85832E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00872E-07 | 0 | 0 |
| D/Y | rs749005996  |
-0.613 | 1.0 | D | 0.701 | 0.508 | 0.791131006835 | gnomAD-2.1.1 | 4.11E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.12E-06 | 0 |
| D/Y | rs749005996 |
-0.613 | 1.0 | D | 0.701 | 0.508 | 0.791131006835 | gnomAD-4.0.0 | 1.37166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80174E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.8434 | likely_pathogenic | 0.7787 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.489107872 | None | None | N |
| D/C | 0.9698 | likely_pathogenic | 0.9613 | pathogenic | -0.038 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/E | 0.8197 | likely_pathogenic | 0.7149 | pathogenic | -0.607 | Destabilizing | 1.0 | D | 0.437 | neutral | N | 0.475750104 | None | None | N |
| D/F | 0.9805 | likely_pathogenic | 0.963 | pathogenic | -0.456 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| D/G | 0.7894 | likely_pathogenic | 0.7184 | pathogenic | -0.749 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.507087223 | None | None | N |
| D/H | 0.9142 | likely_pathogenic | 0.8722 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | N | 0.504022577 | None | None | N |
| D/I | 0.9582 | likely_pathogenic | 0.9274 | pathogenic | 0.232 | Stabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| D/K | 0.9551 | likely_pathogenic | 0.9416 | pathogenic | -0.091 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| D/L | 0.9504 | likely_pathogenic | 0.9238 | pathogenic | 0.232 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| D/M | 0.9801 | likely_pathogenic | 0.9632 | pathogenic | 0.652 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/N | 0.2791 | likely_benign | 0.208 | benign | -0.4 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.470763355 | None | None | N |
| D/P | 0.9606 | likely_pathogenic | 0.9488 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/Q | 0.9508 | likely_pathogenic | 0.9212 | pathogenic | -0.324 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| D/R | 0.962 | likely_pathogenic | 0.949 | pathogenic | -0.091 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| D/S | 0.6359 | likely_pathogenic | 0.5471 | ambiguous | -0.57 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/T | 0.8362 | likely_pathogenic | 0.7266 | pathogenic | -0.348 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | N |
| D/V | 0.8894 | likely_pathogenic | 0.8273 | pathogenic | 0.021 | Stabilizing | 1.0 | D | 0.758 | deleterious | N | 0.501705172 | None | None | N |
| D/W | 0.9939 | likely_pathogenic | 0.9907 | pathogenic | -0.356 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Y | 0.8096 | likely_pathogenic | 0.7576 | pathogenic | -0.235 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | D | 0.539016546 | 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.