Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27867 | 83824;83825;83826 | chr2:178562533;178562532;178562531 | chr2:179427260;179427259;179427258 |
| N2AB | 26226 | 78901;78902;78903 | chr2:178562533;178562532;178562531 | chr2:179427260;179427259;179427258 |
| N2A | 25299 | 76120;76121;76122 | chr2:178562533;178562532;178562531 | chr2:179427260;179427259;179427258 |
| N2B | 18802 | 56629;56630;56631 | chr2:178562533;178562532;178562531 | chr2:179427260;179427259;179427258 |
| Novex-1 | 18927 | 57004;57005;57006 | chr2:178562533;178562532;178562531 | chr2:179427260;179427259;179427258 |
| Novex-2 | 18994 | 57205;57206;57207 | chr2:178562533;178562532;178562531 | chr2:179427260;179427259;179427258 |
| 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/R | rs374119634  |
-1.73 | 1.0 | D | 0.948 | 0.677 | None | gnomAD-2.1.1 | 3.99E-05 | None | None | None | None | N | None | 4.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.88E-05 | 0 |
| P/R | rs374119634 |
-1.73 | 1.0 | D | 0.948 | 0.677 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| P/R | rs374119634 |
-1.73 | 1.0 | D | 0.948 | 0.677 | None | gnomAD-4.0.0 | 1.10547E-04 | None | None | None | None | N | None | 5.35432E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.42537E-04 | 0 | 9.62649E-05 |
| P/S | None | None | 1.0 | D | 0.867 | 0.751 | 0.608747212676 | gnomAD-4.0.0 | 4.79982E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.42483E-04 | 5.7345E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6277 | likely_pathogenic | 0.6219 | pathogenic | -2.367 | Highly Destabilizing | 1.0 | D | 0.828 | deleterious | D | 0.525217246 | None | None | N |
| P/C | 0.9548 | likely_pathogenic | 0.9508 | pathogenic | -2.221 | Highly Destabilizing | 1.0 | D | 0.931 | deleterious | None | None | None | None | N |
| P/D | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -3.387 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| P/E | 0.9961 | likely_pathogenic | 0.9966 | pathogenic | -3.135 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| P/F | 0.998 | likely_pathogenic | 0.9983 | pathogenic | -1.115 | Destabilizing | 1.0 | D | 0.944 | deleterious | None | None | None | None | N |
| P/G | 0.9899 | likely_pathogenic | 0.9889 | pathogenic | -2.879 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| P/H | 0.9962 | likely_pathogenic | 0.9968 | pathogenic | -2.487 | Highly Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.575606445 | None | None | N |
| P/I | 0.7983 | likely_pathogenic | 0.8149 | pathogenic | -0.896 | Destabilizing | 1.0 | D | 0.943 | deleterious | None | None | None | None | N |
| P/K | 0.9979 | likely_pathogenic | 0.9983 | pathogenic | -1.806 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| P/L | 0.8306 | likely_pathogenic | 0.8459 | pathogenic | -0.896 | Destabilizing | 1.0 | D | 0.917 | deleterious | D | 0.562475713 | None | None | N |
| P/M | 0.9655 | likely_pathogenic | 0.9684 | pathogenic | -1.394 | Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| P/N | 0.9983 | likely_pathogenic | 0.9982 | pathogenic | -2.35 | Highly Destabilizing | 1.0 | D | 0.947 | deleterious | None | None | None | None | N |
| P/Q | 0.992 | likely_pathogenic | 0.9932 | pathogenic | -2.106 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| P/R | 0.9932 | likely_pathogenic | 0.9945 | pathogenic | -1.729 | Destabilizing | 1.0 | D | 0.948 | deleterious | D | 0.54860142 | None | None | N |
| P/S | 0.9573 | likely_pathogenic | 0.9588 | pathogenic | -2.842 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.5572487 | None | None | N |
| P/T | 0.855 | likely_pathogenic | 0.859 | pathogenic | -2.458 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | D | 0.545131926 | None | None | N |
| P/V | 0.5741 | likely_pathogenic | 0.5956 | pathogenic | -1.368 | Destabilizing | 1.0 | D | 0.918 | deleterious | None | None | None | None | N |
| P/W | 0.9996 | likely_pathogenic | 0.9997 | pathogenic | -1.627 | Destabilizing | 1.0 | D | 0.925 | deleterious | None | None | None | None | N |
| P/Y | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.393 | Destabilizing | 1.0 | D | 0.946 | 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.