Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16467 | 49624;49625;49626 | chr2:178613884;178613883;178613882 | chr2:179478611;179478610;179478609 |
| N2AB | 14826 | 44701;44702;44703 | chr2:178613884;178613883;178613882 | chr2:179478611;179478610;179478609 |
| N2A | 13899 | 41920;41921;41922 | chr2:178613884;178613883;178613882 | chr2:179478611;179478610;179478609 |
| N2B | 7402 | 22429;22430;22431 | chr2:178613884;178613883;178613882 | chr2:179478611;179478610;179478609 |
| Novex-1 | 7527 | 22804;22805;22806 | chr2:178613884;178613883;178613882 | chr2:179478611;179478610;179478609 |
| Novex-2 | 7594 | 23005;23006;23007 | chr2:178613884;178613883;178613882 | chr2:179478611;179478610;179478609 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs780901860  |
-2.422 | 0.998 | N | 0.593 | 0.412 | 0.610288044756 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| V/A | rs780901860 |
-2.422 | 0.998 | N | 0.593 | 0.412 | 0.610288044756 | gnomAD-4.0.0 | 4.79123E-06 | None | None | None | None | N | None | 0 | 2.2998E-05 | None | 0 | 0 | None | 0 | 0 | 5.7345E-06 | 0 | 0 |
| V/M | rs376161624 |
-0.665 | 0.999 | N | 0.763 | 0.284 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6185 | likely_pathogenic | 0.6136 | pathogenic | -2.337 | Highly Destabilizing | 0.998 | D | 0.593 | neutral | N | 0.482417463 | None | None | N |
| V/C | 0.8982 | likely_pathogenic | 0.889 | pathogenic | -2.262 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| V/D | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -3.037 | Highly Destabilizing | 1.0 | D | 0.862 | deleterious | None | None | None | None | N |
| V/E | 0.9948 | likely_pathogenic | 0.9955 | pathogenic | -2.724 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | D | 0.685033251 | None | None | N |
| V/F | 0.8431 | likely_pathogenic | 0.8709 | pathogenic | -1.396 | Destabilizing | 0.999 | D | 0.859 | deleterious | None | None | None | None | N |
| V/G | 0.9223 | likely_pathogenic | 0.926 | pathogenic | -2.972 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | D | 0.683604943 | None | None | N |
| V/H | 0.9982 | likely_pathogenic | 0.9984 | pathogenic | -2.842 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| V/I | 0.1124 | likely_benign | 0.1137 | benign | -0.507 | Destabilizing | 0.985 | D | 0.515 | neutral | None | None | None | None | N |
| V/K | 0.9964 | likely_pathogenic | 0.9971 | pathogenic | -1.911 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| V/L | 0.4185 | ambiguous | 0.4035 | ambiguous | -0.507 | Destabilizing | 0.434 | N | 0.285 | neutral | N | 0.466978784 | None | None | N |
| V/M | 0.4493 | ambiguous | 0.4956 | ambiguous | -0.92 | Destabilizing | 0.999 | D | 0.763 | deleterious | N | 0.48383627 | None | None | N |
| V/N | 0.9938 | likely_pathogenic | 0.9945 | pathogenic | -2.539 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/P | 0.9977 | likely_pathogenic | 0.9979 | pathogenic | -1.095 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| V/Q | 0.9914 | likely_pathogenic | 0.9923 | pathogenic | -2.193 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/R | 0.9931 | likely_pathogenic | 0.9939 | pathogenic | -2.003 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/S | 0.9474 | likely_pathogenic | 0.9541 | pathogenic | -3.193 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| V/T | 0.8374 | likely_pathogenic | 0.8463 | pathogenic | -2.699 | Highly Destabilizing | 0.998 | D | 0.635 | neutral | None | None | None | None | N |
| V/W | 0.9985 | likely_pathogenic | 0.9988 | pathogenic | -1.897 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| V/Y | 0.9897 | likely_pathogenic | 0.9915 | pathogenic | -1.559 | Destabilizing | 1.0 | D | 0.853 | 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.