Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18175 | 54748;54749;54750 | chr2:178604164;178604163;178604162 | chr2:179468891;179468890;179468889 |
| N2AB | 16534 | 49825;49826;49827 | chr2:178604164;178604163;178604162 | chr2:179468891;179468890;179468889 |
| N2A | 15607 | 47044;47045;47046 | chr2:178604164;178604163;178604162 | chr2:179468891;179468890;179468889 |
| N2B | 9110 | 27553;27554;27555 | chr2:178604164;178604163;178604162 | chr2:179468891;179468890;179468889 |
| Novex-1 | 9235 | 27928;27929;27930 | chr2:178604164;178604163;178604162 | chr2:179468891;179468890;179468889 |
| Novex-2 | 9302 | 28129;28130;28131 | chr2:178604164;178604163;178604162 | chr2:179468891;179468890;179468889 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs776320086  |
-0.547 | 0.003 | N | 0.178 | 0.121 | 0.280987212366 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.66E-05 | 8.92E-06 | 0 |
| V/I | rs776320086 |
-0.547 | 0.003 | N | 0.178 | 0.121 | 0.280987212366 | gnomAD-4.0.0 | 5.4788E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.40052E-06 | 0 | 3.31708E-05 |
| V/L | None | None | 0.075 | N | 0.429 | 0.132 | 0.404733080969 | gnomAD-4.0.0 | 1.3697E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80017E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6244 | likely_pathogenic | 0.525 | ambiguous | -1.615 | Destabilizing | 0.517 | D | 0.593 | neutral | N | 0.436692498 | None | None | N |
| V/C | 0.8657 | likely_pathogenic | 0.8589 | pathogenic | -1.084 | Destabilizing | 0.996 | D | 0.682 | prob.neutral | None | None | None | None | N |
| V/D | 0.9539 | likely_pathogenic | 0.9413 | pathogenic | -1.384 | Destabilizing | 0.983 | D | 0.81 | deleterious | N | 0.517332369 | None | None | N |
| V/E | 0.9051 | likely_pathogenic | 0.887 | pathogenic | -1.313 | Destabilizing | 0.987 | D | 0.776 | deleterious | None | None | None | None | N |
| V/F | 0.6338 | likely_pathogenic | 0.5697 | pathogenic | -1.017 | Destabilizing | 0.901 | D | 0.71 | prob.delet. | N | 0.495183442 | None | None | N |
| V/G | 0.705 | likely_pathogenic | 0.6236 | pathogenic | -2.018 | Highly Destabilizing | 0.949 | D | 0.794 | deleterious | D | 0.524180984 | None | None | N |
| V/H | 0.9727 | likely_pathogenic | 0.9662 | pathogenic | -1.563 | Destabilizing | 0.996 | D | 0.797 | deleterious | None | None | None | None | N |
| V/I | 0.0902 | likely_benign | 0.0829 | benign | -0.574 | Destabilizing | 0.003 | N | 0.178 | neutral | N | 0.405564302 | None | None | N |
| V/K | 0.9386 | likely_pathogenic | 0.9319 | pathogenic | -1.396 | Destabilizing | 0.961 | D | 0.775 | deleterious | None | None | None | None | N |
| V/L | 0.4302 | ambiguous | 0.3748 | ambiguous | -0.574 | Destabilizing | 0.075 | N | 0.429 | neutral | N | 0.447757641 | None | None | N |
| V/M | 0.5343 | ambiguous | 0.4825 | ambiguous | -0.464 | Destabilizing | 0.923 | D | 0.612 | neutral | None | None | None | None | N |
| V/N | 0.8789 | likely_pathogenic | 0.8549 | pathogenic | -1.268 | Destabilizing | 0.987 | D | 0.816 | deleterious | None | None | None | None | N |
| V/P | 0.7279 | likely_pathogenic | 0.6764 | pathogenic | -0.887 | Destabilizing | 0.987 | D | 0.777 | deleterious | None | None | None | None | N |
| V/Q | 0.9267 | likely_pathogenic | 0.9145 | pathogenic | -1.32 | Destabilizing | 0.987 | D | 0.783 | deleterious | None | None | None | None | N |
| V/R | 0.909 | likely_pathogenic | 0.8986 | pathogenic | -0.994 | Destabilizing | 0.987 | D | 0.825 | deleterious | None | None | None | None | N |
| V/S | 0.8118 | likely_pathogenic | 0.7549 | pathogenic | -1.876 | Destabilizing | 0.961 | D | 0.739 | prob.delet. | None | None | None | None | N |
| V/T | 0.7116 | likely_pathogenic | 0.6552 | pathogenic | -1.68 | Destabilizing | 0.775 | D | 0.617 | neutral | None | None | None | None | N |
| V/W | 0.9776 | likely_pathogenic | 0.9702 | pathogenic | -1.296 | Destabilizing | 0.996 | D | 0.759 | deleterious | None | None | None | None | N |
| V/Y | 0.9246 | likely_pathogenic | 0.9026 | pathogenic | -0.983 | Destabilizing | 0.961 | D | 0.719 | prob.delet. | 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.