Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24126 | 72601;72602;72603 | chr2:178573756;178573755;178573754 | chr2:179438483;179438482;179438481 |
| N2AB | 22485 | 67678;67679;67680 | chr2:178573756;178573755;178573754 | chr2:179438483;179438482;179438481 |
| N2A | 21558 | 64897;64898;64899 | chr2:178573756;178573755;178573754 | chr2:179438483;179438482;179438481 |
| N2B | 15061 | 45406;45407;45408 | chr2:178573756;178573755;178573754 | chr2:179438483;179438482;179438481 |
| Novex-1 | 15186 | 45781;45782;45783 | chr2:178573756;178573755;178573754 | chr2:179438483;179438482;179438481 |
| Novex-2 | 15253 | 45982;45983;45984 | chr2:178573756;178573755;178573754 | chr2:179438483;179438482;179438481 |
| 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/H | None | None | 0.999 | D | 0.912 | 0.648 | 0.798961515949 | gnomAD-4.0.0 | 1.66035E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.95849E-06 | 0 | 0 |
| P/R | rs1277679194  |
None | 0.997 | D | 0.906 | 0.635 | 0.797042821937 | gnomAD-4.0.0 | 1.66035E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79611E-05 | None | 0 | 0 | 0 | 0 | 0 |
| P/T | rs1222800053 |
-2.748 | 0.982 | D | 0.839 | 0.661 | 0.74876033247 | gnomAD-2.1.1 | 4.38E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.83E-05 | None | 0 | None | 0 | 0 | 0 |
| P/T | rs1222800053 |
-2.748 | 0.982 | D | 0.839 | 0.661 | 0.74876033247 | gnomAD-4.0.0 | 1.65986E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79595E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2369 | likely_benign | 0.2781 | benign | -2.222 | Highly Destabilizing | 0.885 | D | 0.789 | deleterious | D | 0.574457054 | None | None | N |
| P/C | 0.6515 | likely_pathogenic | 0.6675 | pathogenic | -1.76 | Destabilizing | 0.128 | N | 0.805 | deleterious | None | None | None | None | N |
| P/D | 0.9965 | likely_pathogenic | 0.9962 | pathogenic | -3.172 | Highly Destabilizing | 0.998 | D | 0.833 | deleterious | None | None | None | None | N |
| P/E | 0.9876 | likely_pathogenic | 0.9866 | pathogenic | -3.01 | Highly Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| P/F | 0.9931 | likely_pathogenic | 0.994 | pathogenic | -1.299 | Destabilizing | 0.999 | D | 0.925 | deleterious | None | None | None | None | N |
| P/G | 0.9133 | likely_pathogenic | 0.92 | pathogenic | -2.683 | Highly Destabilizing | 0.993 | D | 0.888 | deleterious | None | None | None | None | N |
| P/H | 0.9869 | likely_pathogenic | 0.9865 | pathogenic | -2.447 | Highly Destabilizing | 0.999 | D | 0.912 | deleterious | D | 0.660731223 | None | None | N |
| P/I | 0.6454 | likely_pathogenic | 0.6802 | pathogenic | -0.944 | Destabilizing | 0.986 | D | 0.923 | deleterious | None | None | None | None | N |
| P/K | 0.9944 | likely_pathogenic | 0.9941 | pathogenic | -2.038 | Highly Destabilizing | 0.998 | D | 0.825 | deleterious | None | None | None | None | N |
| P/L | 0.6442 | likely_pathogenic | 0.6711 | pathogenic | -0.944 | Destabilizing | 0.964 | D | 0.892 | deleterious | D | 0.660327614 | None | None | N |
| P/M | 0.863 | likely_pathogenic | 0.8668 | pathogenic | -0.947 | Destabilizing | 0.999 | D | 0.914 | deleterious | None | None | None | None | N |
| P/N | 0.9886 | likely_pathogenic | 0.9879 | pathogenic | -2.226 | Highly Destabilizing | 0.998 | D | 0.907 | deleterious | None | None | None | None | N |
| P/Q | 0.9712 | likely_pathogenic | 0.9708 | pathogenic | -2.16 | Highly Destabilizing | 0.998 | D | 0.837 | deleterious | None | None | None | None | N |
| P/R | 0.9827 | likely_pathogenic | 0.9833 | pathogenic | -1.688 | Destabilizing | 0.997 | D | 0.906 | deleterious | D | 0.660529419 | None | None | N |
| P/S | 0.6779 | likely_pathogenic | 0.702 | pathogenic | -2.711 | Highly Destabilizing | 0.982 | D | 0.835 | deleterious | D | 0.634789503 | None | None | N |
| P/T | 0.5114 | ambiguous | 0.5493 | ambiguous | -2.441 | Highly Destabilizing | 0.982 | D | 0.839 | deleterious | D | 0.628258532 | None | None | N |
| P/V | 0.3302 | likely_benign | 0.3734 | ambiguous | -1.346 | Destabilizing | 0.986 | D | 0.885 | deleterious | None | None | None | None | N |
| P/W | 0.9984 | likely_pathogenic | 0.9986 | pathogenic | -1.859 | Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| P/Y | 0.9972 | likely_pathogenic | 0.9971 | pathogenic | -1.557 | Destabilizing | 0.999 | D | 0.93 | 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.