Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23320 | 70183;70184;70185 | chr2:178576174;178576173;178576172 | chr2:179440901;179440900;179440899 |
| N2AB | 21679 | 65260;65261;65262 | chr2:178576174;178576173;178576172 | chr2:179440901;179440900;179440899 |
| N2A | 20752 | 62479;62480;62481 | chr2:178576174;178576173;178576172 | chr2:179440901;179440900;179440899 |
| N2B | 14255 | 42988;42989;42990 | chr2:178576174;178576173;178576172 | chr2:179440901;179440900;179440899 |
| Novex-1 | 14380 | 43363;43364;43365 | chr2:178576174;178576173;178576172 | chr2:179440901;179440900;179440899 |
| Novex-2 | 14447 | 43564;43565;43566 | chr2:178576174;178576173;178576172 | chr2:179440901;179440900;179440899 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs756468956  |
-1.288 | 0.999 | N | 0.591 | 0.605 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/S | rs756468956 |
-1.288 | 0.999 | N | 0.591 | 0.605 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs756468956 |
-1.288 | 0.999 | N | 0.591 | 0.605 | None | gnomAD-4.0.0 | 2.47986E-06 | None | None | None | None | N | None | 5.34045E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9811 | likely_pathogenic | 0.9844 | pathogenic | -0.82 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| N/C | 0.8703 | likely_pathogenic | 0.8759 | pathogenic | -0.583 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| N/D | 0.9834 | likely_pathogenic | 0.9829 | pathogenic | -2.155 | Highly Destabilizing | 0.999 | D | 0.606 | neutral | D | 0.522219418 | None | None | N |
| N/E | 0.9973 | likely_pathogenic | 0.9973 | pathogenic | -1.98 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| N/F | 0.9987 | likely_pathogenic | 0.9988 | pathogenic | -0.597 | Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| N/G | 0.957 | likely_pathogenic | 0.9605 | pathogenic | -1.148 | Destabilizing | 0.999 | D | 0.569 | neutral | None | None | None | None | N |
| N/H | 0.9441 | likely_pathogenic | 0.943 | pathogenic | -0.793 | Destabilizing | 1.0 | D | 0.772 | deleterious | D | 0.549731422 | None | None | N |
| N/I | 0.9877 | likely_pathogenic | 0.9884 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.774 | deleterious | D | 0.550238401 | None | None | N |
| N/K | 0.9966 | likely_pathogenic | 0.9966 | pathogenic | -0.317 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.522472908 | None | None | N |
| N/L | 0.9508 | likely_pathogenic | 0.952 | pathogenic | 0.025 | Stabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| N/M | 0.9857 | likely_pathogenic | 0.9876 | pathogenic | 0.234 | Stabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | N |
| N/P | 0.9914 | likely_pathogenic | 0.9908 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| N/Q | 0.9956 | likely_pathogenic | 0.9959 | pathogenic | -1.154 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| N/R | 0.9897 | likely_pathogenic | 0.9896 | pathogenic | -0.308 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| N/S | 0.513 | ambiguous | 0.5387 | ambiguous | -1.15 | Destabilizing | 0.999 | D | 0.591 | neutral | N | 0.50404903 | None | None | N |
| N/T | 0.8641 | likely_pathogenic | 0.8851 | pathogenic | -0.819 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | N | 0.510197414 | None | None | N |
| N/V | 0.979 | likely_pathogenic | 0.9813 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| N/W | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -0.56 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| N/Y | 0.9877 | likely_pathogenic | 0.9873 | pathogenic | -0.165 | Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.549984912 | 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.