Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31873 | 95842;95843;95844 | chr2:178545493;178545492;178545491 | chr2:179410220;179410219;179410218 |
| N2AB | 30232 | 90919;90920;90921 | chr2:178545493;178545492;178545491 | chr2:179410220;179410219;179410218 |
| N2A | 29305 | 88138;88139;88140 | chr2:178545493;178545492;178545491 | chr2:179410220;179410219;179410218 |
| N2B | 22808 | 68647;68648;68649 | chr2:178545493;178545492;178545491 | chr2:179410220;179410219;179410218 |
| Novex-1 | 22933 | 69022;69023;69024 | chr2:178545493;178545492;178545491 | chr2:179410220;179410219;179410218 |
| Novex-2 | 23000 | 69223;69224;69225 | chr2:178545493;178545492;178545491 | chr2:179410220;179410219;179410218 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | rs748974241  |
-1.172 | 0.996 | D | 0.859 | 0.628 | 0.862890512107 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| L/M | rs748974241 |
-1.172 | 0.996 | D | 0.859 | 0.628 | 0.862890512107 | gnomAD-4.0.0 | 1.59174E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85956E-06 | 0 | 0 |
| L/R | rs778060662 |
-1.592 | 0.989 | D | 0.901 | 0.898 | 0.907924906354 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.44E-05 | 0 |
| L/R | rs778060662 |
-1.592 | 0.989 | D | 0.901 | 0.898 | 0.907924906354 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| L/R | rs778060662 |
-1.592 | 0.989 | D | 0.901 | 0.898 | 0.907924906354 | gnomAD-4.0.0 | 1.23955E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56206E-05 | 0 | 1.6107E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9116 | likely_pathogenic | 0.9404 | pathogenic | -2.714 | Highly Destabilizing | 0.895 | D | 0.829 | deleterious | None | None | None | None | N |
| L/C | 0.8524 | likely_pathogenic | 0.8965 | pathogenic | -2.035 | Highly Destabilizing | 0.999 | D | 0.848 | deleterious | None | None | None | None | N |
| L/D | 0.9988 | likely_pathogenic | 0.9991 | pathogenic | -3.024 | Highly Destabilizing | 0.983 | D | 0.912 | deleterious | None | None | None | None | N |
| L/E | 0.9932 | likely_pathogenic | 0.9956 | pathogenic | -2.88 | Highly Destabilizing | 0.983 | D | 0.914 | deleterious | None | None | None | None | N |
| L/F | 0.8262 | likely_pathogenic | 0.8336 | pathogenic | -1.803 | Destabilizing | 0.997 | D | 0.885 | deleterious | None | None | None | None | N |
| L/G | 0.9818 | likely_pathogenic | 0.9877 | pathogenic | -3.205 | Highly Destabilizing | 0.983 | D | 0.911 | deleterious | None | None | None | None | N |
| L/H | 0.9854 | likely_pathogenic | 0.9892 | pathogenic | -2.507 | Highly Destabilizing | 0.999 | D | 0.908 | deleterious | None | None | None | None | N |
| L/I | 0.3172 | likely_benign | 0.3868 | ambiguous | -1.322 | Destabilizing | 0.972 | D | 0.831 | deleterious | None | None | None | None | N |
| L/K | 0.9833 | likely_pathogenic | 0.9889 | pathogenic | -2.133 | Highly Destabilizing | 0.983 | D | 0.909 | deleterious | None | None | None | None | N |
| L/M | 0.4251 | ambiguous | 0.4641 | ambiguous | -1.111 | Destabilizing | 0.996 | D | 0.859 | deleterious | D | 0.60600642 | None | None | N |
| L/N | 0.9869 | likely_pathogenic | 0.9914 | pathogenic | -2.283 | Highly Destabilizing | 0.992 | D | 0.918 | deleterious | None | None | None | None | N |
| L/P | 0.9885 | likely_pathogenic | 0.9898 | pathogenic | -1.765 | Destabilizing | 0.085 | N | 0.748 | deleterious | D | 0.677623856 | None | None | N |
| L/Q | 0.9639 | likely_pathogenic | 0.9734 | pathogenic | -2.306 | Highly Destabilizing | 0.989 | D | 0.912 | deleterious | D | 0.677623856 | None | None | N |
| L/R | 0.9665 | likely_pathogenic | 0.9752 | pathogenic | -1.59 | Destabilizing | 0.989 | D | 0.901 | deleterious | D | 0.661604495 | None | None | N |
| L/S | 0.9853 | likely_pathogenic | 0.9905 | pathogenic | -2.955 | Highly Destabilizing | 0.983 | D | 0.909 | deleterious | None | None | None | None | N |
| L/T | 0.9217 | likely_pathogenic | 0.9532 | pathogenic | -2.675 | Highly Destabilizing | 0.983 | D | 0.866 | deleterious | None | None | None | None | N |
| L/V | 0.2957 | likely_benign | 0.3645 | ambiguous | -1.765 | Destabilizing | 0.928 | D | 0.846 | deleterious | D | 0.604875957 | None | None | N |
| L/W | 0.9845 | likely_pathogenic | 0.9847 | pathogenic | -2.109 | Highly Destabilizing | 0.999 | D | 0.859 | deleterious | None | None | None | None | N |
| L/Y | 0.9811 | likely_pathogenic | 0.9852 | pathogenic | -1.895 | Destabilizing | 0.997 | D | 0.875 | 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.