Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17986 | 54181;54182;54183 | chr2:178605221;178605220;178605219 | chr2:179469948;179469947;179469946 |
| N2AB | 16345 | 49258;49259;49260 | chr2:178605221;178605220;178605219 | chr2:179469948;179469947;179469946 |
| N2A | 15418 | 46477;46478;46479 | chr2:178605221;178605220;178605219 | chr2:179469948;179469947;179469946 |
| N2B | 8921 | 26986;26987;26988 | chr2:178605221;178605220;178605219 | chr2:179469948;179469947;179469946 |
| Novex-1 | 9046 | 27361;27362;27363 | chr2:178605221;178605220;178605219 | chr2:179469948;179469947;179469946 |
| Novex-2 | 9113 | 27562;27563;27564 | chr2:178605221;178605220;178605219 | chr2:179469948;179469947;179469946 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1200347706  |
-2.827 | 0.722 | D | 0.763 | 0.538 | 0.735826198445 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14863E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1200347706 |
-2.827 | 0.722 | D | 0.763 | 0.538 | 0.735826198445 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1200347706 |
-2.827 | 0.722 | D | 0.763 | 0.538 | 0.735826198445 | gnomAD-4.0.0 | 6.58597E-06 | None | None | None | None | N | None | 2.41686E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1293207173 |
None | 0.19 | N | 0.345 | 0.186 | 0.59827724986 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1293207173 |
None | 0.19 | N | 0.345 | 0.186 | 0.59827724986 | gnomAD-4.0.0 | 6.58345E-06 | None | None | None | None | N | None | 0 | 6.56685E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9731 | likely_pathogenic | 0.9786 | pathogenic | -2.415 | Highly Destabilizing | 0.633 | D | 0.687 | prob.neutral | None | None | None | None | N |
| I/C | 0.9631 | likely_pathogenic | 0.9708 | pathogenic | -1.707 | Destabilizing | 0.996 | D | 0.737 | prob.delet. | None | None | None | None | N |
| I/D | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -2.851 | Highly Destabilizing | 0.987 | D | 0.873 | deleterious | None | None | None | None | N |
| I/E | 0.9979 | likely_pathogenic | 0.9982 | pathogenic | -2.601 | Highly Destabilizing | 0.961 | D | 0.875 | deleterious | None | None | None | None | N |
| I/F | 0.4858 | ambiguous | 0.4668 | ambiguous | -1.455 | Destabilizing | 0.901 | D | 0.717 | prob.delet. | N | 0.463609741 | None | None | N |
| I/G | 0.9958 | likely_pathogenic | 0.9967 | pathogenic | -2.959 | Highly Destabilizing | 0.961 | D | 0.864 | deleterious | None | None | None | None | N |
| I/H | 0.9935 | likely_pathogenic | 0.9943 | pathogenic | -2.331 | Highly Destabilizing | 0.996 | D | 0.854 | deleterious | None | None | None | None | N |
| I/K | 0.9956 | likely_pathogenic | 0.9958 | pathogenic | -2.003 | Highly Destabilizing | 0.923 | D | 0.864 | deleterious | None | None | None | None | N |
| I/L | 0.1776 | likely_benign | 0.1891 | benign | -0.836 | Destabilizing | 0.075 | N | 0.347 | neutral | N | 0.433574835 | None | None | N |
| I/M | 0.3134 | likely_benign | 0.3023 | benign | -0.775 | Destabilizing | 0.034 | N | 0.349 | neutral | N | 0.48838326 | None | None | N |
| I/N | 0.9876 | likely_pathogenic | 0.989 | pathogenic | -2.453 | Highly Destabilizing | 0.949 | D | 0.871 | deleterious | N | 0.513320146 | None | None | N |
| I/P | 0.9978 | likely_pathogenic | 0.9982 | pathogenic | -1.345 | Destabilizing | 0.987 | D | 0.87 | deleterious | None | None | None | None | N |
| I/Q | 0.9944 | likely_pathogenic | 0.9949 | pathogenic | -2.276 | Highly Destabilizing | 0.961 | D | 0.873 | deleterious | None | None | None | None | N |
| I/R | 0.9935 | likely_pathogenic | 0.9939 | pathogenic | -1.778 | Destabilizing | 0.923 | D | 0.873 | deleterious | None | None | None | None | N |
| I/S | 0.983 | likely_pathogenic | 0.985 | pathogenic | -3.105 | Highly Destabilizing | 0.901 | D | 0.828 | deleterious | D | 0.524676451 | None | None | N |
| I/T | 0.981 | likely_pathogenic | 0.9841 | pathogenic | -2.697 | Highly Destabilizing | 0.722 | D | 0.763 | deleterious | D | 0.524422962 | None | None | N |
| I/V | 0.1829 | likely_benign | 0.2017 | benign | -1.345 | Destabilizing | 0.19 | N | 0.345 | neutral | N | 0.512086839 | None | None | N |
| I/W | 0.9905 | likely_pathogenic | 0.9897 | pathogenic | -1.81 | Destabilizing | 0.996 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Y | 0.9583 | likely_pathogenic | 0.9554 | pathogenic | -1.497 | Destabilizing | 0.961 | D | 0.743 | 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.