Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23861 | 71806;71807;71808 | chr2:178574551;178574550;178574549 | chr2:179439278;179439277;179439276 |
| N2AB | 22220 | 66883;66884;66885 | chr2:178574551;178574550;178574549 | chr2:179439278;179439277;179439276 |
| N2A | 21293 | 64102;64103;64104 | chr2:178574551;178574550;178574549 | chr2:179439278;179439277;179439276 |
| N2B | 14796 | 44611;44612;44613 | chr2:178574551;178574550;178574549 | chr2:179439278;179439277;179439276 |
| Novex-1 | 14921 | 44986;44987;44988 | chr2:178574551;178574550;178574549 | chr2:179439278;179439277;179439276 |
| Novex-2 | 14988 | 45187;45188;45189 | chr2:178574551;178574550;178574549 | chr2:179439278;179439277;179439276 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs2154171639  |
None | 1.0 | D | 0.877 | 0.936 | 0.856361183982 | 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 |
| Y/H | rs759611506 |
-3.076 | 1.0 | D | 0.809 | 0.894 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.29182E-04 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| Y/H | rs759611506 |
-3.076 | 1.0 | D | 0.809 | 0.894 | None | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44781E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs759611506 |
-3.076 | 1.0 | D | 0.809 | 0.894 | None | gnomAD-4.0.0 | 9.29683E-06 | None | None | None | None | N | None | 1.73551E-04 | 0 | None | 0 | 0 | None | 1.56216E-05 | 0 | 8.47721E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9968 | likely_pathogenic | 0.9956 | pathogenic | -3.844 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| Y/C | 0.863 | likely_pathogenic | 0.8395 | pathogenic | -2.188 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.655369999 | None | None | N |
| Y/D | 0.9971 | likely_pathogenic | 0.9956 | pathogenic | -3.999 | Highly Destabilizing | 1.0 | D | 0.914 | deleterious | D | 0.671591165 | None | None | N |
| Y/E | 0.9992 | likely_pathogenic | 0.9987 | pathogenic | -3.8 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| Y/F | 0.176 | likely_benign | 0.1896 | benign | -1.728 | Destabilizing | 0.999 | D | 0.641 | neutral | D | 0.55976996 | None | None | N |
| Y/G | 0.992 | likely_pathogenic | 0.9874 | pathogenic | -4.208 | Highly Destabilizing | 1.0 | D | 0.923 | deleterious | None | None | None | None | N |
| Y/H | 0.9632 | likely_pathogenic | 0.9577 | pathogenic | -2.838 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | D | 0.654966391 | None | None | N |
| Y/I | 0.9731 | likely_pathogenic | 0.9667 | pathogenic | -2.584 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| Y/K | 0.998 | likely_pathogenic | 0.997 | pathogenic | -2.82 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| Y/L | 0.9607 | likely_pathogenic | 0.9452 | pathogenic | -2.584 | Highly Destabilizing | 0.999 | D | 0.743 | deleterious | None | None | None | None | N |
| Y/M | 0.9835 | likely_pathogenic | 0.9794 | pathogenic | -2.232 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| Y/N | 0.9747 | likely_pathogenic | 0.9652 | pathogenic | -3.545 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | D | 0.67138936 | None | None | N |
| Y/P | 0.9995 | likely_pathogenic | 0.9992 | pathogenic | -3.025 | Highly Destabilizing | 1.0 | D | 0.939 | deleterious | None | None | None | None | N |
| Y/Q | 0.9975 | likely_pathogenic | 0.9965 | pathogenic | -3.318 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| Y/R | 0.9929 | likely_pathogenic | 0.9905 | pathogenic | -2.478 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| Y/S | 0.9863 | likely_pathogenic | 0.9808 | pathogenic | -3.839 | Highly Destabilizing | 1.0 | D | 0.901 | deleterious | D | 0.67138936 | None | None | N |
| Y/T | 0.9961 | likely_pathogenic | 0.9942 | pathogenic | -3.539 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| Y/V | 0.9619 | likely_pathogenic | 0.9539 | pathogenic | -3.025 | Highly Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | N |
| Y/W | 0.7868 | likely_pathogenic | 0.7647 | pathogenic | -0.962 | Destabilizing | 1.0 | D | 0.796 | 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.