Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33465 | 100618;100619;100620 | chr2:178536354;178536353;178536352 | chr2:179401081;179401080;179401079 |
| N2AB | 31824 | 95695;95696;95697 | chr2:178536354;178536353;178536352 | chr2:179401081;179401080;179401079 |
| N2A | 30897 | 92914;92915;92916 | chr2:178536354;178536353;178536352 | chr2:179401081;179401080;179401079 |
| N2B | 24400 | 73423;73424;73425 | chr2:178536354;178536353;178536352 | chr2:179401081;179401080;179401079 |
| Novex-1 | 24525 | 73798;73799;73800 | chr2:178536354;178536353;178536352 | chr2:179401081;179401080;179401079 |
| Novex-2 | 24592 | 73999;74000;74001 | chr2:178536354;178536353;178536352 | chr2:179401081;179401080;179401079 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1691494185  |
None | 0.999 | N | 0.681 | 0.575 | 0.45563089846 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/L | rs1691494185 |
None | 0.999 | N | 0.681 | 0.575 | 0.45563089846 | gnomAD-4.0.0 | 6.57194E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46994E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.9974 | likely_pathogenic | 0.9981 | pathogenic | -2.922 | Highly Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | N |
| F/C | 0.9799 | likely_pathogenic | 0.9795 | pathogenic | -1.775 | Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.547796093 | None | None | N |
| F/D | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -3.721 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| F/E | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -3.469 | Highly Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| F/G | 0.9979 | likely_pathogenic | 0.9984 | pathogenic | -3.401 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| F/H | 0.9968 | likely_pathogenic | 0.9972 | pathogenic | -2.303 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| F/I | 0.9274 | likely_pathogenic | 0.9346 | pathogenic | -1.331 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.504200388 | None | None | N |
| F/K | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -2.476 | Highly Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| F/L | 0.9929 | likely_pathogenic | 0.9932 | pathogenic | -1.331 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | N | 0.49411153 | None | None | N |
| F/M | 0.9715 | likely_pathogenic | 0.9721 | pathogenic | -1.004 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| F/N | 0.9982 | likely_pathogenic | 0.9987 | pathogenic | -3.187 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | N |
| F/P | 0.9999 | likely_pathogenic | 1.0 | pathogenic | -1.878 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| F/Q | 0.9994 | likely_pathogenic | 0.9997 | pathogenic | -2.989 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| F/R | 0.9991 | likely_pathogenic | 0.9995 | pathogenic | -2.229 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| F/S | 0.9977 | likely_pathogenic | 0.9984 | pathogenic | -3.669 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | D | 0.547796093 | None | None | N |
| F/T | 0.9976 | likely_pathogenic | 0.9984 | pathogenic | -3.288 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| F/V | 0.9418 | likely_pathogenic | 0.9476 | pathogenic | -1.878 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | N | 0.489041739 | None | None | N |
| F/W | 0.9266 | likely_pathogenic | 0.9307 | pathogenic | -0.569 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| F/Y | 0.6095 | likely_pathogenic | 0.6134 | pathogenic | -1.025 | Destabilizing | 0.999 | D | 0.579 | neutral | N | 0.501926344 | 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.