Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21521 | 64786;64787;64788 | chr2:178585183;178585182;178585181 | chr2:179449910;179449909;179449908 |
| N2AB | 19880 | 59863;59864;59865 | chr2:178585183;178585182;178585181 | chr2:179449910;179449909;179449908 |
| N2A | 18953 | 57082;57083;57084 | chr2:178585183;178585182;178585181 | chr2:179449910;179449909;179449908 |
| N2B | 12456 | 37591;37592;37593 | chr2:178585183;178585182;178585181 | chr2:179449910;179449909;179449908 |
| Novex-1 | 12581 | 37966;37967;37968 | chr2:178585183;178585182;178585181 | chr2:179449910;179449909;179449908 |
| Novex-2 | 12648 | 38167;38168;38169 | chr2:178585183;178585182;178585181 | chr2:179449910;179449909;179449908 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/F | rs766887868  |
-0.67 | 0.934 | N | 0.686 | 0.331 | 0.665958451526 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| S/F | rs766887868 |
-0.67 | 0.934 | N | 0.686 | 0.331 | 0.665958451526 | gnomAD-4.0.0 | 1.59226E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86053E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0834 | likely_benign | 0.0845 | benign | -0.54 | Destabilizing | 0.454 | N | 0.445 | neutral | N | 0.511548121 | None | None | N |
| S/C | 0.0956 | likely_benign | 0.0989 | benign | -0.444 | Destabilizing | 0.997 | D | 0.593 | neutral | D | 0.531790108 | None | None | N |
| S/D | 0.5416 | ambiguous | 0.5687 | pathogenic | -1.052 | Destabilizing | 0.842 | D | 0.621 | neutral | None | None | None | None | N |
| S/E | 0.5545 | ambiguous | 0.5763 | pathogenic | -1.053 | Destabilizing | 0.842 | D | 0.597 | neutral | None | None | None | None | N |
| S/F | 0.1935 | likely_benign | 0.1982 | benign | -0.762 | Destabilizing | 0.934 | D | 0.686 | prob.neutral | N | 0.496773457 | None | None | N |
| S/G | 0.1142 | likely_benign | 0.1233 | benign | -0.788 | Destabilizing | 0.842 | D | 0.553 | neutral | None | None | None | None | N |
| S/H | 0.3021 | likely_benign | 0.3035 | benign | -1.376 | Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | N |
| S/I | 0.1686 | likely_benign | 0.1732 | benign | 0.013 | Stabilizing | 0.728 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/K | 0.6066 | likely_pathogenic | 0.6422 | pathogenic | -0.838 | Destabilizing | 0.842 | D | 0.589 | neutral | None | None | None | None | N |
| S/L | 0.1015 | likely_benign | 0.1035 | benign | 0.013 | Stabilizing | 0.016 | N | 0.39 | neutral | None | None | None | None | N |
| S/M | 0.1869 | likely_benign | 0.1917 | benign | 0.424 | Stabilizing | 0.949 | D | 0.635 | neutral | None | None | None | None | N |
| S/N | 0.1655 | likely_benign | 0.1812 | benign | -0.904 | Destabilizing | 0.842 | D | 0.601 | neutral | None | None | None | None | N |
| S/P | 0.7735 | likely_pathogenic | 0.786 | pathogenic | -0.137 | Destabilizing | 0.966 | D | 0.661 | neutral | N | 0.498596479 | None | None | N |
| S/Q | 0.4284 | ambiguous | 0.4511 | ambiguous | -1.109 | Destabilizing | 0.974 | D | 0.637 | neutral | None | None | None | None | N |
| S/R | 0.5287 | ambiguous | 0.5727 | pathogenic | -0.679 | Destabilizing | 0.949 | D | 0.661 | neutral | None | None | None | None | N |
| S/T | 0.0748 | likely_benign | 0.0735 | benign | -0.783 | Destabilizing | 0.022 | N | 0.181 | neutral | N | 0.427084085 | None | None | N |
| S/V | 0.1561 | likely_benign | 0.1577 | benign | -0.137 | Destabilizing | 0.728 | D | 0.615 | neutral | None | None | None | None | N |
| S/W | 0.4049 | ambiguous | 0.4017 | ambiguous | -0.822 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1899 | likely_benign | 0.1886 | benign | -0.522 | Destabilizing | 0.989 | D | 0.689 | prob.neutral | N | 0.486191104 | 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.