Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21360 | 64303;64304;64305 | chr2:178587133;178587132;178587131 | chr2:179451860;179451859;179451858 |
| N2AB | 19719 | 59380;59381;59382 | chr2:178587133;178587132;178587131 | chr2:179451860;179451859;179451858 |
| N2A | 18792 | 56599;56600;56601 | chr2:178587133;178587132;178587131 | chr2:179451860;179451859;179451858 |
| N2B | 12295 | 37108;37109;37110 | chr2:178587133;178587132;178587131 | chr2:179451860;179451859;179451858 |
| Novex-1 | 12420 | 37483;37484;37485 | chr2:178587133;178587132;178587131 | chr2:179451860;179451859;179451858 |
| Novex-2 | 12487 | 37684;37685;37686 | chr2:178587133;178587132;178587131 | chr2:179451860;179451859;179451858 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 1.0 | N | 0.792 | 0.332 | 0.398872588132 | gnomAD-4.0.0 | 1.5924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77377E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs778085017  |
-1.968 | 1.0 | N | 0.749 | 0.308 | 0.275215494804 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/T | rs778085017 |
-1.968 | 1.0 | N | 0.749 | 0.308 | 0.275215494804 | gnomAD-4.0.0 | 1.5924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43312E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6203 | likely_pathogenic | 0.6214 | pathogenic | -1.929 | Destabilizing | 1.0 | D | 0.737 | deleterious | None | None | None | None | N |
| A/D | 0.9941 | likely_pathogenic | 0.9919 | pathogenic | -2.821 | Highly Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| A/E | 0.9901 | likely_pathogenic | 0.9858 | pathogenic | -2.655 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.500865344 | None | None | N |
| A/F | 0.9191 | likely_pathogenic | 0.9047 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| A/G | 0.5417 | ambiguous | 0.5149 | ambiguous | -1.809 | Destabilizing | 0.999 | D | 0.562 | neutral | N | 0.484482609 | None | None | N |
| A/H | 0.9899 | likely_pathogenic | 0.9868 | pathogenic | -1.85 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| A/I | 0.6195 | likely_pathogenic | 0.5272 | ambiguous | -0.424 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| A/K | 0.9968 | likely_pathogenic | 0.9951 | pathogenic | -1.383 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| A/L | 0.5916 | likely_pathogenic | 0.5222 | ambiguous | -0.424 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| A/M | 0.7513 | likely_pathogenic | 0.7392 | pathogenic | -0.965 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| A/N | 0.9717 | likely_pathogenic | 0.9637 | pathogenic | -1.746 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| A/P | 0.7956 | likely_pathogenic | 0.6689 | pathogenic | -0.723 | Destabilizing | 1.0 | D | 0.792 | deleterious | N | 0.480861758 | None | None | N |
| A/Q | 0.9776 | likely_pathogenic | 0.9709 | pathogenic | -1.65 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| A/R | 0.9875 | likely_pathogenic | 0.981 | pathogenic | -1.354 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/S | 0.3518 | ambiguous | 0.3255 | benign | -2.101 | Highly Destabilizing | 0.999 | D | 0.603 | neutral | N | 0.48372214 | None | None | N |
| A/T | 0.4939 | ambiguous | 0.4047 | ambiguous | -1.827 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.506741656 | None | None | N |
| A/V | 0.3633 | ambiguous | 0.2884 | benign | -0.723 | Destabilizing | 0.999 | D | 0.652 | prob.neutral | N | 0.483400649 | None | None | N |
| A/W | 0.9952 | likely_pathogenic | 0.9936 | pathogenic | -1.552 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| A/Y | 0.9796 | likely_pathogenic | 0.9755 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.839 | 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.