Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24448 | 73567;73568;73569 | chr2:178572790;178572789;178572788 | chr2:179437517;179437516;179437515 |
| N2AB | 22807 | 68644;68645;68646 | chr2:178572790;178572789;178572788 | chr2:179437517;179437516;179437515 |
| N2A | 21880 | 65863;65864;65865 | chr2:178572790;178572789;178572788 | chr2:179437517;179437516;179437515 |
| N2B | 15383 | 46372;46373;46374 | chr2:178572790;178572789;178572788 | chr2:179437517;179437516;179437515 |
| Novex-1 | 15508 | 46747;46748;46749 | chr2:178572790;178572789;178572788 | chr2:179437517;179437516;179437515 |
| Novex-2 | 15575 | 46948;46949;46950 | chr2:178572790;178572789;178572788 | chr2:179437517;179437516;179437515 |
| 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/H | None | None | 0.999 | D | 0.815 | 0.747 | 0.932804463114 | gnomAD-4.0.0 | 3.42162E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49795E-06 | 0 | 0 |
| L/V | rs1400578707  |
-1.219 | 0.618 | D | 0.692 | 0.508 | 0.541105671861 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.51042E-04 | None | 0 | None | 0 | 0 | 0 |
| L/V | rs1400578707 |
-1.219 | 0.618 | D | 0.692 | 0.508 | 0.541105671861 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs1400578707 |
-1.219 | 0.618 | D | 0.692 | 0.508 | 0.541105671861 | gnomAD-4.0.0 | 3.84493E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.28686E-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 | 0.9782 | likely_pathogenic | 0.9737 | pathogenic | -2.121 | Highly Destabilizing | 0.968 | D | 0.718 | prob.delet. | None | None | None | None | N |
| L/C | 0.9586 | likely_pathogenic | 0.9524 | pathogenic | -1.622 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| L/D | 0.9997 | likely_pathogenic | 0.9995 | pathogenic | -2.816 | Highly Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| L/E | 0.9985 | likely_pathogenic | 0.9979 | pathogenic | -2.567 | Highly Destabilizing | 0.998 | D | 0.831 | deleterious | None | None | None | None | N |
| L/F | 0.751 | likely_pathogenic | 0.7146 | pathogenic | -1.479 | Destabilizing | 0.988 | D | 0.768 | deleterious | D | 0.527152292 | None | None | N |
| L/G | 0.997 | likely_pathogenic | 0.9961 | pathogenic | -2.566 | Highly Destabilizing | 0.995 | D | 0.842 | deleterious | None | None | None | None | N |
| L/H | 0.9949 | likely_pathogenic | 0.9929 | pathogenic | -2.246 | Highly Destabilizing | 0.999 | D | 0.815 | deleterious | D | 0.619166622 | None | None | N |
| L/I | 0.1624 | likely_benign | 0.1509 | benign | -0.796 | Destabilizing | 0.142 | N | 0.423 | neutral | D | 0.551912413 | None | None | N |
| L/K | 0.9971 | likely_pathogenic | 0.9957 | pathogenic | -1.889 | Destabilizing | 0.995 | D | 0.829 | deleterious | None | None | None | None | N |
| L/M | 0.3245 | likely_benign | 0.3116 | benign | -0.909 | Destabilizing | 0.991 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/N | 0.9978 | likely_pathogenic | 0.9966 | pathogenic | -2.482 | Highly Destabilizing | 0.998 | D | 0.834 | deleterious | None | None | None | None | N |
| L/P | 0.9981 | likely_pathogenic | 0.9972 | pathogenic | -1.229 | Destabilizing | 0.998 | D | 0.832 | deleterious | D | 0.619166622 | None | None | N |
| L/Q | 0.9939 | likely_pathogenic | 0.9917 | pathogenic | -2.183 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| L/R | 0.9949 | likely_pathogenic | 0.9926 | pathogenic | -2.0 | Highly Destabilizing | 0.998 | D | 0.821 | deleterious | D | 0.619166622 | None | None | N |
| L/S | 0.9973 | likely_pathogenic | 0.9965 | pathogenic | -2.919 | Highly Destabilizing | 0.995 | D | 0.832 | deleterious | None | None | None | None | N |
| L/T | 0.99 | likely_pathogenic | 0.9878 | pathogenic | -2.528 | Highly Destabilizing | 0.991 | D | 0.777 | deleterious | None | None | None | None | N |
| L/V | 0.3108 | likely_benign | 0.2947 | benign | -1.229 | Destabilizing | 0.618 | D | 0.692 | prob.neutral | D | 0.569867353 | None | None | N |
| L/W | 0.9864 | likely_pathogenic | 0.9811 | pathogenic | -1.747 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | N |
| L/Y | 0.9804 | likely_pathogenic | 0.9733 | pathogenic | -1.521 | Destabilizing | 0.995 | D | 0.775 | 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.