Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25713 | 77362;77363;77364 | chr2:178568995;178568994;178568993 | chr2:179433722;179433721;179433720 |
| N2AB | 24072 | 72439;72440;72441 | chr2:178568995;178568994;178568993 | chr2:179433722;179433721;179433720 |
| N2A | 23145 | 69658;69659;69660 | chr2:178568995;178568994;178568993 | chr2:179433722;179433721;179433720 |
| N2B | 16648 | 50167;50168;50169 | chr2:178568995;178568994;178568993 | chr2:179433722;179433721;179433720 |
| Novex-1 | 16773 | 50542;50543;50544 | chr2:178568995;178568994;178568993 | chr2:179433722;179433721;179433720 |
| Novex-2 | 16840 | 50743;50744;50745 | chr2:178568995;178568994;178568993 | chr2:179433722;179433721;179433720 |
| 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/D | rs1484287814  |
-0.704 | 0.55 | N | 0.271 | 0.17 | 0.139678290688 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| N/D | rs1484287814 |
-0.704 | 0.55 | N | 0.271 | 0.17 | 0.139678290688 | gnomAD-4.0.0 | 1.59197E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43332E-05 | 0 |
| N/S | rs774259989 |
None | 0.046 | N | 0.096 | 0.133 | 0.104622674875 | gnomAD-4.0.0 | 1.36868E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79921E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3215 | likely_benign | 0.3188 | benign | -0.525 | Destabilizing | 0.098 | N | 0.319 | neutral | None | None | None | None | N |
| N/C | 0.3609 | ambiguous | 0.3557 | ambiguous | 0.242 | Stabilizing | 0.998 | D | 0.353 | neutral | None | None | None | None | N |
| N/D | 0.1874 | likely_benign | 0.1614 | benign | -0.866 | Destabilizing | 0.55 | D | 0.271 | neutral | N | 0.46778341 | None | None | N |
| N/E | 0.4595 | ambiguous | 0.4221 | ambiguous | -0.867 | Destabilizing | 0.69 | D | 0.245 | neutral | None | None | None | None | N |
| N/F | 0.5789 | likely_pathogenic | 0.5702 | pathogenic | -0.841 | Destabilizing | 0.993 | D | 0.385 | neutral | None | None | None | None | N |
| N/G | 0.3617 | ambiguous | 0.3603 | ambiguous | -0.739 | Destabilizing | 0.849 | D | 0.256 | neutral | None | None | None | None | N |
| N/H | 0.1135 | likely_benign | 0.111 | benign | -0.828 | Destabilizing | 0.04 | N | 0.168 | neutral | N | 0.497703672 | None | None | N |
| N/I | 0.3926 | ambiguous | 0.3867 | ambiguous | -0.032 | Destabilizing | 0.952 | D | 0.422 | neutral | N | 0.499173958 | None | None | N |
| N/K | 0.3254 | likely_benign | 0.2876 | benign | -0.036 | Destabilizing | 0.17 | N | 0.106 | neutral | N | 0.487756037 | None | None | N |
| N/L | 0.3461 | ambiguous | 0.3262 | benign | -0.032 | Destabilizing | 0.883 | D | 0.416 | neutral | None | None | None | None | N |
| N/M | 0.3796 | ambiguous | 0.3724 | ambiguous | 0.7 | Stabilizing | 0.994 | D | 0.339 | neutral | None | None | None | None | N |
| N/P | 0.9285 | likely_pathogenic | 0.9202 | pathogenic | -0.169 | Destabilizing | 0.92 | D | 0.399 | neutral | None | None | None | None | N |
| N/Q | 0.3475 | ambiguous | 0.3293 | benign | -0.823 | Destabilizing | 0.883 | D | 0.355 | neutral | None | None | None | None | N |
| N/R | 0.3885 | ambiguous | 0.3608 | ambiguous | 0.13 | Stabilizing | 0.91 | D | 0.277 | neutral | None | None | None | None | N |
| N/S | 0.094 | likely_benign | 0.0974 | benign | -0.427 | Destabilizing | 0.046 | N | 0.096 | neutral | N | 0.43145725 | None | None | N |
| N/T | 0.1311 | likely_benign | 0.132 | benign | -0.285 | Destabilizing | 0.025 | N | 0.101 | neutral | N | 0.407865527 | None | None | N |
| N/V | 0.3788 | ambiguous | 0.3816 | ambiguous | -0.169 | Destabilizing | 0.388 | N | 0.439 | neutral | None | None | None | None | N |
| N/W | 0.8155 | likely_pathogenic | 0.8145 | pathogenic | -0.729 | Destabilizing | 0.999 | D | 0.429 | neutral | None | None | None | None | N |
| N/Y | 0.196 | likely_benign | 0.1918 | benign | -0.447 | Destabilizing | 0.982 | D | 0.397 | neutral | N | 0.484032218 | 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.