Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25885 | 77878;77879;77880 | chr2:178568479;178568478;178568477 | chr2:179433206;179433205;179433204 |
| N2AB | 24244 | 72955;72956;72957 | chr2:178568479;178568478;178568477 | chr2:179433206;179433205;179433204 |
| N2A | 23317 | 70174;70175;70176 | chr2:178568479;178568478;178568477 | chr2:179433206;179433205;179433204 |
| N2B | 16820 | 50683;50684;50685 | chr2:178568479;178568478;178568477 | chr2:179433206;179433205;179433204 |
| Novex-1 | 16945 | 51058;51059;51060 | chr2:178568479;178568478;178568477 | chr2:179433206;179433205;179433204 |
| Novex-2 | 17012 | 51259;51260;51261 | chr2:178568479;178568478;178568477 | chr2:179433206;179433205;179433204 |
| 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 | rs199514898  |
-2.427 | 0.201 | N | 0.65 | 0.42 | None | gnomAD-2.1.1 | 1.03728E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 1.59987E-04 | 1.80152E-04 | 0 |
| I/T | rs199514898 |
-2.427 | 0.201 | N | 0.65 | 0.42 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 1.88822E-04 | 0 | 7.36E-05 | 0 | 0 |
| I/T | rs199514898 |
-2.427 | 0.201 | N | 0.65 | 0.42 | None | gnomAD-4.0.0 | 2.17578E-04 | None | None | None | None | N | None | 5.34174E-05 | 0 | None | 0 | 0 | None | 2.50117E-04 | 0 | 2.73826E-04 | 2.19621E-05 | 9.61076E-05 |
| I/V | None | None | 0.001 | N | 0.271 | 0.049 | 0.238705975628 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.8669 | likely_pathogenic | 0.8786 | pathogenic | -2.525 | Highly Destabilizing | 0.25 | N | 0.614 | neutral | None | None | None | None | N |
| I/C | 0.9398 | likely_pathogenic | 0.9389 | pathogenic | -2.07 | Highly Destabilizing | 0.947 | D | 0.729 | prob.delet. | None | None | None | None | N |
| I/D | 0.9979 | likely_pathogenic | 0.9986 | pathogenic | -2.336 | Highly Destabilizing | 0.826 | D | 0.799 | deleterious | None | None | None | None | N |
| I/E | 0.9951 | likely_pathogenic | 0.9963 | pathogenic | -2.083 | Highly Destabilizing | 0.826 | D | 0.791 | deleterious | None | None | None | None | N |
| I/F | 0.4629 | ambiguous | 0.4547 | ambiguous | -1.483 | Destabilizing | 0.638 | D | 0.71 | prob.delet. | N | 0.477381221 | None | None | N |
| I/G | 0.9856 | likely_pathogenic | 0.9877 | pathogenic | -3.11 | Highly Destabilizing | 0.826 | D | 0.786 | deleterious | None | None | None | None | N |
| I/H | 0.9932 | likely_pathogenic | 0.9942 | pathogenic | -2.454 | Highly Destabilizing | 0.982 | D | 0.795 | deleterious | None | None | None | None | N |
| I/K | 0.9919 | likely_pathogenic | 0.9936 | pathogenic | -1.812 | Destabilizing | 0.826 | D | 0.791 | deleterious | None | None | None | None | N |
| I/L | 0.255 | likely_benign | 0.2292 | benign | -0.829 | Destabilizing | 0.043 | N | 0.419 | neutral | N | 0.430426516 | None | None | N |
| I/M | 0.2339 | likely_benign | 0.232 | benign | -0.976 | Destabilizing | 0.638 | D | 0.712 | prob.delet. | N | 0.4891556 | None | None | N |
| I/N | 0.9749 | likely_pathogenic | 0.9818 | pathogenic | -2.195 | Highly Destabilizing | 0.916 | D | 0.811 | deleterious | N | 0.490169558 | None | None | N |
| I/P | 0.9935 | likely_pathogenic | 0.9948 | pathogenic | -1.375 | Destabilizing | 0.826 | D | 0.807 | deleterious | None | None | None | None | N |
| I/Q | 0.9928 | likely_pathogenic | 0.9941 | pathogenic | -1.998 | Destabilizing | 0.935 | D | 0.81 | deleterious | None | None | None | None | N |
| I/R | 0.9875 | likely_pathogenic | 0.9898 | pathogenic | -1.636 | Destabilizing | 0.826 | D | 0.811 | deleterious | None | None | None | None | N |
| I/S | 0.965 | likely_pathogenic | 0.9731 | pathogenic | -3.031 | Highly Destabilizing | 0.638 | D | 0.707 | prob.neutral | N | 0.478395179 | None | None | N |
| I/T | 0.8453 | likely_pathogenic | 0.8688 | pathogenic | -2.608 | Highly Destabilizing | 0.201 | N | 0.65 | neutral | N | 0.489916069 | None | None | N |
| I/V | 0.0867 | likely_benign | 0.0789 | benign | -1.375 | Destabilizing | 0.001 | N | 0.271 | neutral | N | 0.376358037 | None | None | N |
| I/W | 0.9847 | likely_pathogenic | 0.9861 | pathogenic | -1.748 | Destabilizing | 0.982 | D | 0.755 | deleterious | None | None | None | None | N |
| I/Y | 0.9398 | likely_pathogenic | 0.9502 | pathogenic | -1.482 | Destabilizing | 0.826 | D | 0.73 | 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.