Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26138 | 78637;78638;78639 | chr2:178567720;178567719;178567718 | chr2:179432447;179432446;179432445 |
| N2AB | 24497 | 73714;73715;73716 | chr2:178567720;178567719;178567718 | chr2:179432447;179432446;179432445 |
| N2A | 23570 | 70933;70934;70935 | chr2:178567720;178567719;178567718 | chr2:179432447;179432446;179432445 |
| N2B | 17073 | 51442;51443;51444 | chr2:178567720;178567719;178567718 | chr2:179432447;179432446;179432445 |
| Novex-1 | 17198 | 51817;51818;51819 | chr2:178567720;178567719;178567718 | chr2:179432447;179432446;179432445 |
| Novex-2 | 17265 | 52018;52019;52020 | chr2:178567720;178567719;178567718 | chr2:179432447;179432446;179432445 |
| 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/D | rs373587432  |
-0.95 | 1.0 | N | 0.772 | 0.544 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| A/D | rs373587432 |
-0.95 | 1.0 | N | 0.772 | 0.544 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| A/D | rs373587432 |
-0.95 | 1.0 | N | 0.772 | 0.544 | None | gnomAD-4.0.0 | 1.05446E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.64636E-04 | 1.27257E-05 | 0 | 1.60287E-05 |
| A/S | None | None | 1.0 | N | 0.553 | 0.269 | 0.336400405673 | gnomAD-4.0.0 | 6.84865E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00323E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6623 | likely_pathogenic | 0.6502 | pathogenic | -0.347 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | I |
| A/D | 0.9812 | likely_pathogenic | 0.9761 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.772 | deleterious | N | 0.489885935 | None | None | I |
| A/E | 0.9729 | likely_pathogenic | 0.9691 | pathogenic | -0.244 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| A/F | 0.9377 | likely_pathogenic | 0.9229 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| A/G | 0.3988 | ambiguous | 0.3655 | ambiguous | -0.774 | Destabilizing | 1.0 | D | 0.564 | neutral | N | 0.481745633 | None | None | I |
| A/H | 0.9823 | likely_pathogenic | 0.9768 | pathogenic | -0.986 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| A/I | 0.8444 | likely_pathogenic | 0.8169 | pathogenic | 0.416 | Stabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | I |
| A/K | 0.9953 | likely_pathogenic | 0.9937 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | I |
| A/L | 0.7963 | likely_pathogenic | 0.7796 | pathogenic | 0.416 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| A/M | 0.8068 | likely_pathogenic | 0.7776 | pathogenic | 0.253 | Stabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | I |
| A/N | 0.9348 | likely_pathogenic | 0.9137 | pathogenic | -0.48 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | I |
| A/P | 0.9881 | likely_pathogenic | 0.9859 | pathogenic | 0.181 | Stabilizing | 1.0 | D | 0.779 | deleterious | N | 0.490139424 | None | None | I |
| A/Q | 0.9648 | likely_pathogenic | 0.959 | pathogenic | -0.408 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| A/R | 0.9888 | likely_pathogenic | 0.9864 | pathogenic | -0.553 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| A/S | 0.2639 | likely_benign | 0.245 | benign | -0.955 | Destabilizing | 1.0 | D | 0.553 | neutral | N | 0.467983018 | None | None | I |
| A/T | 0.4164 | ambiguous | 0.3722 | ambiguous | -0.75 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.475389304 | None | None | I |
| A/V | 0.4898 | ambiguous | 0.4577 | ambiguous | 0.181 | Stabilizing | 1.0 | D | 0.601 | neutral | N | 0.440502729 | None | None | I |
| A/W | 0.9954 | likely_pathogenic | 0.994 | pathogenic | -0.888 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| A/Y | 0.9672 | likely_pathogenic | 0.9582 | pathogenic | -0.319 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
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.