Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26213 | 78862;78863;78864 | chr2:178567495;178567494;178567493 | chr2:179432222;179432221;179432220 |
| N2AB | 24572 | 73939;73940;73941 | chr2:178567495;178567494;178567493 | chr2:179432222;179432221;179432220 |
| N2A | 23645 | 71158;71159;71160 | chr2:178567495;178567494;178567493 | chr2:179432222;179432221;179432220 |
| N2B | 17148 | 51667;51668;51669 | chr2:178567495;178567494;178567493 | chr2:179432222;179432221;179432220 |
| Novex-1 | 17273 | 52042;52043;52044 | chr2:178567495;178567494;178567493 | chr2:179432222;179432221;179432220 |
| Novex-2 | 17340 | 52243;52244;52245 | chr2:178567495;178567494;178567493 | chr2:179432222;179432221;179432220 |
| 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/F | rs1553594441  |
None | 0.999 | N | 0.781 | 0.373 | 0.68219128047 | gnomAD-4.0.0 | 6.84532E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99692E-06 | 0 | 0 |
| L/P | rs2154166338 |
None | 1.0 | D | 0.859 | 0.856 | 0.910442507312 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93424E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs2154166338 |
None | 1.0 | D | 0.859 | 0.856 | 0.910442507312 | gnomAD-4.0.0 | 2.56412E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.86003E-05 | None | 0 | 0 | 0 | 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 | 0.9171 | likely_pathogenic | 0.905 | pathogenic | -1.359 | Destabilizing | 0.998 | D | 0.748 | deleterious | None | None | None | None | N |
| L/C | 0.9063 | likely_pathogenic | 0.8868 | pathogenic | -1.191 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -2.299 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| L/E | 0.9952 | likely_pathogenic | 0.9946 | pathogenic | -2.091 | Highly Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| L/F | 0.5549 | ambiguous | 0.4561 | ambiguous | -1.024 | Destabilizing | 0.999 | D | 0.781 | deleterious | N | 0.510452043 | None | None | N |
| L/G | 0.9909 | likely_pathogenic | 0.989 | pathogenic | -1.718 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/H | 0.9885 | likely_pathogenic | 0.9867 | pathogenic | -1.969 | Destabilizing | 1.0 | D | 0.832 | deleterious | D | 0.632864336 | None | None | N |
| L/I | 0.1047 | likely_benign | 0.1042 | benign | -0.286 | Destabilizing | 0.884 | D | 0.407 | neutral | N | 0.515591102 | None | None | N |
| L/K | 0.9921 | likely_pathogenic | 0.9914 | pathogenic | -1.346 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/M | 0.2465 | likely_benign | 0.1946 | benign | -0.728 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| L/N | 0.9967 | likely_pathogenic | 0.9959 | pathogenic | -1.965 | Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| L/P | 0.993 | likely_pathogenic | 0.9914 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.632864336 | None | None | N |
| L/Q | 0.9836 | likely_pathogenic | 0.9805 | pathogenic | -1.582 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| L/R | 0.9857 | likely_pathogenic | 0.9849 | pathogenic | -1.772 | Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.632864336 | None | None | N |
| L/S | 0.9926 | likely_pathogenic | 0.991 | pathogenic | -2.133 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| L/T | 0.957 | likely_pathogenic | 0.9514 | pathogenic | -1.81 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| L/V | 0.1623 | likely_benign | 0.1635 | benign | -0.638 | Destabilizing | 0.981 | D | 0.706 | prob.neutral | D | 0.568938694 | None | None | N |
| L/W | 0.9317 | likely_pathogenic | 0.9075 | pathogenic | -1.336 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| L/Y | 0.9588 | likely_pathogenic | 0.9447 | pathogenic | -1.159 | Destabilizing | 1.0 | D | 0.789 | 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.