Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1895 | 5908;5909;5910 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
| N2AB | 1895 | 5908;5909;5910 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
| N2A | 1895 | 5908;5909;5910 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
| N2B | 1849 | 5770;5771;5772 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
| Novex-1 | 1849 | 5770;5771;5772 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
| Novex-2 | 1849 | 5770;5771;5772 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
| Novex-3 | 1895 | 5908;5909;5910 | chr2:178776181;178776180;178776179 | chr2:179640908;179640907;179640906 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/P | rs766694270  |
-1.057 | 0.912 | D | 0.74 | 0.503 | 0.520267005839 | gnomAD-2.1.1 | 2.79E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.29E-05 | 1.63239E-04 |
| H/P | rs766694270 |
-1.057 | 0.912 | D | 0.74 | 0.503 | 0.520267005839 | gnomAD-4.0.0 | 1.11337E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.42833E-05 | 0 | 6.04303E-05 |
| H/Y | rs794729577 |
0.661 | None | N | 0.341 | 0.155 | 0.254244900254 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| H/Y | rs794729577 |
0.661 | None | N | 0.341 | 0.155 | 0.254244900254 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| H/Y | rs794729577 |
0.661 | None | N | 0.341 | 0.155 | 0.254244900254 | gnomAD-4.0.0 | 1.23917E-05 | None | None | None | None | N | None | 1.33486E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61017E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.61 | likely_pathogenic | 0.6159 | pathogenic | -1.898 | Destabilizing | 0.388 | N | 0.72 | prob.delet. | None | None | None | None | N |
| H/C | 0.2323 | likely_benign | 0.236 | benign | -0.81 | Destabilizing | 0.981 | D | 0.729 | prob.delet. | None | None | None | None | N |
| H/D | 0.8356 | likely_pathogenic | 0.8353 | pathogenic | -1.777 | Destabilizing | 0.492 | N | 0.693 | prob.neutral | D | 0.592747983 | None | None | N |
| H/E | 0.835 | likely_pathogenic | 0.8365 | pathogenic | -1.567 | Destabilizing | 0.563 | D | 0.653 | neutral | None | None | None | None | N |
| H/F | 0.2809 | likely_benign | 0.2722 | benign | 0.062 | Stabilizing | 0.241 | N | 0.662 | neutral | None | None | None | None | N |
| H/G | 0.8081 | likely_pathogenic | 0.808 | pathogenic | -2.31 | Highly Destabilizing | 0.563 | D | 0.747 | deleterious | None | None | None | None | N |
| H/I | 0.5969 | likely_pathogenic | 0.5761 | pathogenic | -0.658 | Destabilizing | 0.69 | D | 0.759 | deleterious | None | None | None | None | N |
| H/K | 0.8922 | likely_pathogenic | 0.8857 | pathogenic | -0.931 | Destabilizing | 0.388 | N | 0.693 | prob.neutral | None | None | None | None | N |
| H/L | 0.2871 | likely_benign | 0.2703 | benign | -0.658 | Destabilizing | 0.193 | N | 0.739 | prob.delet. | N | 0.499106973 | None | None | N |
| H/M | 0.685 | likely_pathogenic | 0.6857 | pathogenic | -0.761 | Destabilizing | 0.932 | D | 0.719 | prob.delet. | None | None | None | None | N |
| H/N | 0.2766 | likely_benign | 0.2651 | benign | -1.761 | Destabilizing | 0.492 | N | 0.665 | neutral | N | 0.510144931 | None | None | N |
| H/P | 0.8629 | likely_pathogenic | 0.8505 | pathogenic | -1.065 | Destabilizing | 0.912 | D | 0.74 | deleterious | D | 0.55211498 | None | None | N |
| H/Q | 0.5226 | ambiguous | 0.5069 | ambiguous | -1.385 | Destabilizing | 0.773 | D | 0.657 | neutral | N | 0.508477382 | None | None | N |
| H/R | 0.6303 | likely_pathogenic | 0.6075 | pathogenic | -0.988 | Destabilizing | 0.492 | N | 0.662 | neutral | N | 0.511912347 | None | None | N |
| H/S | 0.4701 | ambiguous | 0.4726 | ambiguous | -1.918 | Destabilizing | 0.388 | N | 0.676 | prob.neutral | None | None | None | None | N |
| H/T | 0.6031 | likely_pathogenic | 0.5914 | pathogenic | -1.594 | Destabilizing | 0.563 | D | 0.762 | deleterious | None | None | None | None | N |
| H/V | 0.5311 | ambiguous | 0.5156 | ambiguous | -1.065 | Destabilizing | 0.388 | N | 0.764 | deleterious | None | None | None | None | N |
| H/W | 0.4739 | ambiguous | 0.477 | ambiguous | 0.734 | Stabilizing | 0.818 | D | 0.718 | prob.delet. | None | None | None | None | N |
| H/Y | 0.0718 | likely_benign | 0.0693 | benign | 0.473 | Stabilizing | None | N | 0.341 | neutral | N | 0.478630034 | 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.