Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23459 | 70600;70601;70602 | chr2:178575757;178575756;178575755 | chr2:179440484;179440483;179440482 |
| N2AB | 21818 | 65677;65678;65679 | chr2:178575757;178575756;178575755 | chr2:179440484;179440483;179440482 |
| N2A | 20891 | 62896;62897;62898 | chr2:178575757;178575756;178575755 | chr2:179440484;179440483;179440482 |
| N2B | 14394 | 43405;43406;43407 | chr2:178575757;178575756;178575755 | chr2:179440484;179440483;179440482 |
| Novex-1 | 14519 | 43780;43781;43782 | chr2:178575757;178575756;178575755 | chr2:179440484;179440483;179440482 |
| Novex-2 | 14586 | 43981;43982;43983 | chr2:178575757;178575756;178575755 | chr2:179440484;179440483;179440482 |
| 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 | rs776457502  |
-0.247 | 1.0 | D | 0.887 | 0.694 | 0.659120768314 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| P/L | rs776457502 |
-0.247 | 1.0 | D | 0.887 | 0.694 | 0.659120768314 | gnomAD-4.0.0 | 4.79033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29733E-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 | 0.9583 | likely_pathogenic | 0.9764 | pathogenic | -1.798 | Destabilizing | 1.0 | D | 0.821 | deleterious | D | 0.529655839 | None | None | N |
| P/C | 0.9955 | likely_pathogenic | 0.9975 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.832 | deleterious | None | None | None | None | N |
| P/D | 0.9993 | likely_pathogenic | 0.9996 | pathogenic | -1.92 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| P/E | 0.9987 | likely_pathogenic | 0.9993 | pathogenic | -1.782 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | N |
| P/F | 0.9997 | likely_pathogenic | 0.9999 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| P/G | 0.9952 | likely_pathogenic | 0.9965 | pathogenic | -2.258 | Highly Destabilizing | 1.0 | D | 0.878 | deleterious | None | None | None | None | N |
| P/H | 0.9979 | likely_pathogenic | 0.999 | pathogenic | -1.859 | Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.550584477 | None | None | N |
| P/I | 0.9975 | likely_pathogenic | 0.9988 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| P/K | 0.9995 | likely_pathogenic | 0.9997 | pathogenic | -1.59 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| P/L | 0.9835 | likely_pathogenic | 0.9916 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.548810051 | None | None | N |
| P/M | 0.9987 | likely_pathogenic | 0.9994 | pathogenic | -0.434 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | N |
| P/N | 0.9987 | likely_pathogenic | 0.9992 | pathogenic | -1.634 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| P/Q | 0.9978 | likely_pathogenic | 0.9989 | pathogenic | -1.602 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| P/R | 0.9981 | likely_pathogenic | 0.999 | pathogenic | -1.253 | Destabilizing | 1.0 | D | 0.876 | deleterious | D | 0.534201742 | None | None | N |
| P/S | 0.9878 | likely_pathogenic | 0.9933 | pathogenic | -2.234 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | N | 0.511956431 | None | None | N |
| P/T | 0.9908 | likely_pathogenic | 0.9953 | pathogenic | -1.964 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.541430218 | None | None | N |
| P/V | 0.9908 | likely_pathogenic | 0.9953 | pathogenic | -0.943 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| P/W | 0.9999 | likely_pathogenic | 1.0 | pathogenic | -1.491 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | N |
| P/Y | 0.9997 | likely_pathogenic | 0.9999 | pathogenic | -1.128 | Destabilizing | 1.0 | D | 0.876 | 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.