Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17487 | 52684;52685;52686 | chr2:178608424;178608423;178608422 | chr2:179473151;179473150;179473149 |
| N2AB | 15846 | 47761;47762;47763 | chr2:178608424;178608423;178608422 | chr2:179473151;179473150;179473149 |
| N2A | 14919 | 44980;44981;44982 | chr2:178608424;178608423;178608422 | chr2:179473151;179473150;179473149 |
| N2B | 8422 | 25489;25490;25491 | chr2:178608424;178608423;178608422 | chr2:179473151;179473150;179473149 |
| Novex-1 | 8547 | 25864;25865;25866 | chr2:178608424;178608423;178608422 | chr2:179473151;179473150;179473149 |
| Novex-2 | 8614 | 26065;26066;26067 | chr2:178608424;178608423;178608422 | chr2:179473151;179473150;179473149 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs371758040  |
-1.707 | 0.994 | N | 0.778 | 0.538 | None | gnomAD-2.1.1 | 1.66E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.68E-05 | 0 |
| M/T | rs371758040 |
-1.707 | 0.994 | N | 0.778 | 0.538 | None | gnomAD-4.0.0 | 2.81355E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.69494E-05 | 0 | 0 |
| M/V | None | None | 0.985 | N | 0.521 | 0.431 | 0.319686207203 | 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 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7577 | likely_pathogenic | 0.757 | pathogenic | -2.111 | Highly Destabilizing | 0.989 | D | 0.692 | prob.neutral | None | None | None | None | N |
| M/C | 0.7717 | likely_pathogenic | 0.8079 | pathogenic | -2.745 | Highly Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| M/D | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -2.235 | Highly Destabilizing | 0.999 | D | 0.813 | deleterious | None | None | None | None | N |
| M/E | 0.9916 | likely_pathogenic | 0.9923 | pathogenic | -1.996 | Destabilizing | 0.999 | D | 0.786 | deleterious | None | None | None | None | N |
| M/F | 0.7949 | likely_pathogenic | 0.8021 | pathogenic | -0.747 | Destabilizing | 0.999 | D | 0.716 | prob.delet. | None | None | None | None | N |
| M/G | 0.9752 | likely_pathogenic | 0.9752 | pathogenic | -2.593 | Highly Destabilizing | 0.995 | D | 0.757 | deleterious | None | None | None | None | N |
| M/H | 0.9923 | likely_pathogenic | 0.9934 | pathogenic | -2.354 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| M/I | 0.7437 | likely_pathogenic | 0.7501 | pathogenic | -0.726 | Destabilizing | 0.985 | D | 0.635 | neutral | N | 0.431705179 | None | None | N |
| M/K | 0.9809 | likely_pathogenic | 0.9841 | pathogenic | -1.38 | Destabilizing | 0.994 | D | 0.783 | deleterious | N | 0.501096061 | None | None | N |
| M/L | 0.4356 | ambiguous | 0.4544 | ambiguous | -0.726 | Destabilizing | 0.927 | D | 0.417 | neutral | N | 0.460406359 | None | None | N |
| M/N | 0.9903 | likely_pathogenic | 0.9911 | pathogenic | -1.84 | Destabilizing | 0.999 | D | 0.795 | deleterious | None | None | None | None | N |
| M/P | 0.9986 | likely_pathogenic | 0.9988 | pathogenic | -1.17 | Destabilizing | 0.999 | D | 0.797 | deleterious | None | None | None | None | N |
| M/Q | 0.9187 | likely_pathogenic | 0.9266 | pathogenic | -1.502 | Destabilizing | 0.999 | D | 0.735 | prob.delet. | None | None | None | None | N |
| M/R | 0.9755 | likely_pathogenic | 0.9795 | pathogenic | -1.587 | Destabilizing | 0.998 | D | 0.825 | deleterious | N | 0.501096061 | None | None | N |
| M/S | 0.9199 | likely_pathogenic | 0.9216 | pathogenic | -2.375 | Highly Destabilizing | 0.995 | D | 0.76 | deleterious | None | None | None | None | N |
| M/T | 0.9185 | likely_pathogenic | 0.9206 | pathogenic | -1.998 | Destabilizing | 0.994 | D | 0.778 | deleterious | N | 0.489232777 | None | None | N |
| M/V | 0.249 | likely_benign | 0.2405 | benign | -1.17 | Destabilizing | 0.985 | D | 0.521 | neutral | N | 0.399515403 | None | None | N |
| M/W | 0.9942 | likely_pathogenic | 0.9948 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| M/Y | 0.9822 | likely_pathogenic | 0.9848 | pathogenic | -1.037 | Destabilizing | 0.999 | D | 0.821 | 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.