Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16140 | 48643;48644;48645 | chr2:178615683;178615682;178615681 | chr2:179480410;179480409;179480408 |
| N2AB | 14499 | 43720;43721;43722 | chr2:178615683;178615682;178615681 | chr2:179480410;179480409;179480408 |
| N2A | 13572 | 40939;40940;40941 | chr2:178615683;178615682;178615681 | chr2:179480410;179480409;179480408 |
| N2B | 7075 | 21448;21449;21450 | chr2:178615683;178615682;178615681 | chr2:179480410;179480409;179480408 |
| Novex-1 | 7200 | 21823;21824;21825 | chr2:178615683;178615682;178615681 | chr2:179480410;179480409;179480408 |
| Novex-2 | 7267 | 22024;22025;22026 | chr2:178615683;178615682;178615681 | chr2:179480410;179480409;179480408 |
| 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/L | None | None | 1.0 | D | 0.805 | 0.488 | 0.656830896108 | gnomAD-4.0.0 | 1.59393E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86421E-06 | 0 | 0 |
| P/S | rs1219372837  |
-1.261 | 1.0 | D | 0.74 | 0.444 | 0.373173300195 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1219372837 |
-1.261 | 1.0 | D | 0.74 | 0.444 | 0.373173300195 | gnomAD-4.0.0 | 1.36939E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00059E-07 | 0 | 1.65843E-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 | 0.0951 | likely_benign | 0.1095 | benign | -1.458 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | D | 0.560207563 | None | None | N |
| P/C | 0.6417 | likely_pathogenic | 0.6998 | pathogenic | -0.802 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| P/D | 0.7879 | likely_pathogenic | 0.8403 | pathogenic | -1.346 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| P/E | 0.6168 | likely_pathogenic | 0.7022 | pathogenic | -1.383 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| P/F | 0.6022 | likely_pathogenic | 0.668 | pathogenic | -1.245 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| P/G | 0.5113 | ambiguous | 0.5789 | pathogenic | -1.733 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| P/H | 0.5164 | ambiguous | 0.6108 | pathogenic | -1.228 | Destabilizing | 1.0 | D | 0.797 | deleterious | D | 0.696075558 | None | None | N |
| P/I | 0.5168 | ambiguous | 0.6052 | pathogenic | -0.816 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/K | 0.8038 | likely_pathogenic | 0.8697 | pathogenic | -1.188 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| P/L | 0.2571 | likely_benign | 0.3501 | ambiguous | -0.816 | Destabilizing | 1.0 | D | 0.805 | deleterious | D | 0.677260891 | None | None | N |
| P/M | 0.4575 | ambiguous | 0.5414 | ambiguous | -0.536 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/N | 0.6933 | likely_pathogenic | 0.757 | pathogenic | -0.882 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| P/Q | 0.5038 | ambiguous | 0.61 | pathogenic | -1.121 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| P/R | 0.6638 | likely_pathogenic | 0.769 | pathogenic | -0.561 | Destabilizing | 1.0 | D | 0.829 | deleterious | D | 0.679223158 | None | None | N |
| P/S | 0.2526 | likely_benign | 0.3033 | benign | -1.329 | Destabilizing | 1.0 | D | 0.74 | deleterious | D | 0.590709048 | None | None | N |
| P/T | 0.2355 | likely_benign | 0.3019 | benign | -1.267 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | D | 0.609080515 | None | None | N |
| P/V | 0.3465 | ambiguous | 0.4209 | ambiguous | -0.996 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| P/W | 0.8239 | likely_pathogenic | 0.8761 | pathogenic | -1.382 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| P/Y | 0.6306 | likely_pathogenic | 0.6921 | pathogenic | -1.127 | Destabilizing | 1.0 | D | 0.845 | 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.