Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13850 | 41773;41774;41775 | chr2:178636023;178636022;178636021 | chr2:179500750;179500749;179500748 |
| N2AB | 12209 | 36850;36851;36852 | chr2:178636023;178636022;178636021 | chr2:179500750;179500749;179500748 |
| N2A | 11282 | 34069;34070;34071 | chr2:178636023;178636022;178636021 | chr2:179500750;179500749;179500748 |
| N2B | 4785 | 14578;14579;14580 | chr2:178636023;178636022;178636021 | chr2:179500750;179500749;179500748 |
| Novex-1 | 4910 | 14953;14954;14955 | chr2:178636023;178636022;178636021 | chr2:179500750;179500749;179500748 |
| Novex-2 | 4977 | 15154;15155;15156 | chr2:178636023;178636022;178636021 | chr2:179500750;179500749;179500748 |
| 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/F | None | None | 0.999 | D | 0.543 | 0.473 | 0.376745185316 | 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 | rs774281208  |
-2.172 | 1.0 | D | 0.804 | 0.562 | 0.361758802978 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs774281208 |
-2.172 | 1.0 | D | 0.804 | 0.562 | 0.361758802978 | gnomAD-4.0.0 | 1.59305E-06 | None | None | None | None | N | None | 5.6638E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9983 | likely_pathogenic | 0.9984 | pathogenic | -2.589 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| Y/C | 0.9652 | likely_pathogenic | 0.9666 | pathogenic | -2.25 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | D | 0.59398618 | None | None | N |
| Y/D | 0.9993 | likely_pathogenic | 0.9989 | pathogenic | -2.431 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | D | 0.59398618 | None | None | N |
| Y/E | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -2.2 | Highly Destabilizing | 1.0 | D | 0.912 | deleterious | None | None | None | None | N |
| Y/F | 0.3606 | ambiguous | 0.404 | ambiguous | -1.028 | Destabilizing | 0.999 | D | 0.543 | neutral | D | 0.527345895 | None | None | N |
| Y/G | 0.9975 | likely_pathogenic | 0.9968 | pathogenic | -3.04 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| Y/H | 0.9941 | likely_pathogenic | 0.9926 | pathogenic | -1.998 | Destabilizing | 1.0 | D | 0.804 | deleterious | D | 0.59398618 | None | None | N |
| Y/I | 0.9565 | likely_pathogenic | 0.974 | pathogenic | -1.114 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| Y/K | 0.9997 | likely_pathogenic | 0.9995 | pathogenic | -2.05 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| Y/L | 0.9208 | likely_pathogenic | 0.9398 | pathogenic | -1.114 | Destabilizing | 0.999 | D | 0.688 | prob.delet. | None | None | None | None | N |
| Y/M | 0.9896 | likely_pathogenic | 0.9911 | pathogenic | -1.275 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | N |
| Y/N | 0.9963 | likely_pathogenic | 0.9945 | pathogenic | -2.82 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.59398618 | None | None | N |
| Y/P | 0.9994 | likely_pathogenic | 0.9993 | pathogenic | -1.618 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | N |
| Y/Q | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -2.442 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| Y/R | 0.9983 | likely_pathogenic | 0.9977 | pathogenic | -2.067 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| Y/S | 0.9962 | likely_pathogenic | 0.9949 | pathogenic | -3.355 | Highly Destabilizing | 1.0 | D | 0.907 | deleterious | D | 0.59398618 | None | None | N |
| Y/T | 0.9982 | likely_pathogenic | 0.9982 | pathogenic | -2.982 | Highly Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| Y/V | 0.9221 | likely_pathogenic | 0.9509 | pathogenic | -1.618 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/W | 0.8608 | likely_pathogenic | 0.8659 | pathogenic | -0.365 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | 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.