Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33684 | 101275;101276;101277 | chr2:178535565;178535564;178535563 | chr2:179400292;179400291;179400290 |
| N2AB | 32043 | 96352;96353;96354 | chr2:178535565;178535564;178535563 | chr2:179400292;179400291;179400290 |
| N2A | 31116 | 93571;93572;93573 | chr2:178535565;178535564;178535563 | chr2:179400292;179400291;179400290 |
| N2B | 24619 | 74080;74081;74082 | chr2:178535565;178535564;178535563 | chr2:179400292;179400291;179400290 |
| Novex-1 | 24744 | 74455;74456;74457 | chr2:178535565;178535564;178535563 | chr2:179400292;179400291;179400290 |
| Novex-2 | 24811 | 74656;74657;74658 | chr2:178535565;178535564;178535563 | chr2:179400292;179400291;179400290 |
| 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 | None | -1.47 | 1.0 | N | 0.781 | 0.409 | 0.558850992237 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.65E-05 | 8.88E-06 | 0 |
| L/M | None | -1.47 | 1.0 | N | 0.781 | 0.409 | 0.558850992237 | gnomAD-4.0.0 | 6.1578E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87343E-05 | 0 | 7.19566E-06 | 0 | 0 |
| L/V | rs775824162  |
None | 0.637 | N | 0.316 | 0.131 | 0.297375071883 | gnomAD-4.0.0 | 2.7368E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59783E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9714 | likely_pathogenic | 0.9425 | pathogenic | -2.969 | Highly Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| L/C | 0.9565 | likely_pathogenic | 0.9258 | pathogenic | -2.462 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9993 | pathogenic | -3.61 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/E | 0.9979 | likely_pathogenic | 0.9948 | pathogenic | -3.293 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/F | 0.8578 | likely_pathogenic | 0.6922 | pathogenic | -1.79 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| L/G | 0.9967 | likely_pathogenic | 0.9931 | pathogenic | -3.607 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| L/H | 0.9971 | likely_pathogenic | 0.9923 | pathogenic | -3.176 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| L/I | 0.1707 | likely_benign | 0.1107 | benign | -1.061 | Destabilizing | 0.965 | D | 0.631 | neutral | None | None | None | None | N |
| L/K | 0.9965 | likely_pathogenic | 0.9912 | pathogenic | -2.378 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| L/M | 0.4248 | ambiguous | 0.2844 | benign | -1.242 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.500070374 | None | None | N |
| L/N | 0.9981 | likely_pathogenic | 0.9954 | pathogenic | -3.026 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| L/P | 0.999 | likely_pathogenic | 0.9973 | pathogenic | -1.685 | Destabilizing | 1.0 | D | 0.87 | deleterious | N | 0.512351732 | None | None | N |
| L/Q | 0.9952 | likely_pathogenic | 0.9874 | pathogenic | -2.721 | Highly Destabilizing | 1.0 | D | 0.87 | deleterious | N | 0.512351732 | None | None | N |
| L/R | 0.9934 | likely_pathogenic | 0.9842 | pathogenic | -2.29 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | N | 0.512351732 | None | None | N |
| L/S | 0.9979 | likely_pathogenic | 0.9946 | pathogenic | -3.707 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/T | 0.9739 | likely_pathogenic | 0.9428 | pathogenic | -3.216 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/V | 0.1808 | likely_benign | 0.1335 | benign | -1.685 | Destabilizing | 0.637 | D | 0.316 | neutral | N | 0.444813336 | None | None | N |
| L/W | 0.9876 | likely_pathogenic | 0.9592 | pathogenic | -2.207 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| L/Y | 0.9899 | likely_pathogenic | 0.9715 | pathogenic | -1.981 | Destabilizing | 1.0 | D | 0.823 | 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.