Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27173 | 81742;81743;81744 | chr2:178564615;178564614;178564613 | chr2:179429342;179429341;179429340 |
| N2AB | 25532 | 76819;76820;76821 | chr2:178564615;178564614;178564613 | chr2:179429342;179429341;179429340 |
| N2A | 24605 | 74038;74039;74040 | chr2:178564615;178564614;178564613 | chr2:179429342;179429341;179429340 |
| N2B | 18108 | 54547;54548;54549 | chr2:178564615;178564614;178564613 | chr2:179429342;179429341;179429340 |
| Novex-1 | 18233 | 54922;54923;54924 | chr2:178564615;178564614;178564613 | chr2:179429342;179429341;179429340 |
| Novex-2 | 18300 | 55123;55124;55125 | chr2:178564615;178564614;178564613 | chr2:179429342;179429341;179429340 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs754325718  |
-1.674 | 1.0 | N | 0.85 | 0.274 | None | gnomAD-2.1.1 | 6.44E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 3.60144E-04 | 5.48E-05 | 1.40726E-04 |
| P/A | rs754325718 |
-1.674 | 1.0 | N | 0.85 | 0.274 | None | gnomAD-3.1.2 | 1.24972E-04 | None | None | None | None | N | None | 0 | 2.62433E-04 | 0 | 0 | 0 | None | 1.03774E-03 | 0 | 5.88E-05 | 0 | 0 |
| P/A | rs754325718 |
-1.674 | 1.0 | N | 0.85 | 0.274 | None | gnomAD-4.0.0 | 6.9423E-05 | None | None | None | None | N | None | 0 | 6.67334E-05 | None | 0 | 0 | None | 6.09623E-04 | 0 | 5.59486E-05 | 0 | 4.80477E-05 |
| P/L | rs766831675 |
None | 1.0 | N | 0.902 | 0.519 | 0.698133738195 | gnomAD-4.0.0 | 1.09495E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.25938E-05 | 0 | 3.31411E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0848 | likely_benign | 0.0759 | benign | -1.224 | Destabilizing | 1.0 | D | 0.85 | deleterious | N | 0.494137718 | None | None | N |
| P/C | 0.5709 | likely_pathogenic | 0.5407 | ambiguous | -0.971 | Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | N |
| P/D | 0.9111 | likely_pathogenic | 0.877 | pathogenic | -1.805 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| P/E | 0.6051 | likely_pathogenic | 0.537 | ambiguous | -1.881 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| P/F | 0.7742 | likely_pathogenic | 0.704 | pathogenic | -1.438 | Destabilizing | 1.0 | D | 0.926 | deleterious | None | None | None | None | N |
| P/G | 0.611 | likely_pathogenic | 0.5794 | pathogenic | -1.435 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| P/H | 0.4509 | ambiguous | 0.3909 | ambiguous | -0.972 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| P/I | 0.4692 | ambiguous | 0.3992 | ambiguous | -0.767 | Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| P/K | 0.4131 | ambiguous | 0.3777 | ambiguous | -0.914 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| P/L | 0.3018 | likely_benign | 0.245 | benign | -0.767 | Destabilizing | 1.0 | D | 0.902 | deleterious | N | 0.52052067 | None | None | N |
| P/M | 0.5453 | ambiguous | 0.4723 | ambiguous | -0.432 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| P/N | 0.755 | likely_pathogenic | 0.6922 | pathogenic | -0.762 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| P/Q | 0.3292 | likely_benign | 0.282 | benign | -1.114 | Destabilizing | 1.0 | D | 0.859 | deleterious | N | 0.511010789 | None | None | N |
| P/R | 0.286 | likely_benign | 0.2628 | benign | -0.297 | Destabilizing | 1.0 | D | 0.919 | deleterious | N | 0.501313552 | None | None | N |
| P/S | 0.2384 | likely_benign | 0.2054 | benign | -1.112 | Destabilizing | 1.0 | D | 0.865 | deleterious | N | 0.497425985 | None | None | N |
| P/T | 0.246 | likely_benign | 0.2114 | benign | -1.098 | Destabilizing | 1.0 | D | 0.855 | deleterious | N | 0.510467811 | None | None | N |
| P/V | 0.3209 | likely_benign | 0.2739 | benign | -0.887 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| P/W | 0.9205 | likely_pathogenic | 0.8912 | pathogenic | -1.55 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| P/Y | 0.7693 | likely_pathogenic | 0.7169 | pathogenic | -1.22 | Destabilizing | 1.0 | D | 0.935 | 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.