Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13842 | 41749;41750;41751 | chr2:178636047;178636046;178636045 | chr2:179500774;179500773;179500772 |
| N2AB | 12201 | 36826;36827;36828 | chr2:178636047;178636046;178636045 | chr2:179500774;179500773;179500772 |
| N2A | 11274 | 34045;34046;34047 | chr2:178636047;178636046;178636045 | chr2:179500774;179500773;179500772 |
| N2B | 4777 | 14554;14555;14556 | chr2:178636047;178636046;178636045 | chr2:179500774;179500773;179500772 |
| Novex-1 | 4902 | 14929;14930;14931 | chr2:178636047;178636046;178636045 | chr2:179500774;179500773;179500772 |
| Novex-2 | 4969 | 15130;15131;15132 | chr2:178636047;178636046;178636045 | chr2:179500774;179500773;179500772 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | None | None | 0.002 | N | 0.184 | 0.098 | 0.0806252709748 | gnomAD-4.0.0 | 6.8441E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99667E-07 | 0 | 0 |
| A/V | rs1231962760  |
-0.315 | 0.379 | N | 0.643 | 0.268 | 0.185906805712 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.96E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/V | rs1231962760 |
-0.315 | 0.379 | N | 0.643 | 0.268 | 0.185906805712 | gnomAD-4.0.0 | 1.5924E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76917E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5901 | likely_pathogenic | 0.575 | pathogenic | -1.848 | Destabilizing | 0.992 | D | 0.686 | prob.delet. | None | None | None | None | N |
| A/D | 0.9815 | likely_pathogenic | 0.988 | pathogenic | -2.941 | Highly Destabilizing | 0.617 | D | 0.72 | deleterious | None | None | None | None | N |
| A/E | 0.9716 | likely_pathogenic | 0.9812 | pathogenic | -2.869 | Highly Destabilizing | 0.549 | D | 0.719 | prob.delet. | N | 0.400725842 | None | None | N |
| A/F | 0.9419 | likely_pathogenic | 0.9687 | pathogenic | -1.079 | Destabilizing | 0.92 | D | 0.785 | deleterious | None | None | None | None | N |
| A/G | 0.4724 | ambiguous | 0.5268 | ambiguous | -1.486 | Destabilizing | 0.201 | N | 0.598 | neutral | N | 0.400725842 | None | None | N |
| A/H | 0.9822 | likely_pathogenic | 0.9878 | pathogenic | -1.573 | Destabilizing | 0.977 | D | 0.795 | deleterious | None | None | None | None | N |
| A/I | 0.6028 | likely_pathogenic | 0.7339 | pathogenic | -0.367 | Destabilizing | 0.85 | D | 0.737 | deleterious | None | None | None | None | N |
| A/K | 0.9908 | likely_pathogenic | 0.9948 | pathogenic | -1.511 | Destabilizing | 0.447 | N | 0.732 | deleterious | None | None | None | None | N |
| A/L | 0.6289 | likely_pathogenic | 0.7265 | pathogenic | -0.367 | Destabilizing | 0.447 | N | 0.702 | prob.delet. | None | None | None | None | N |
| A/M | 0.6708 | likely_pathogenic | 0.7662 | pathogenic | -0.634 | Destabilizing | 0.977 | D | 0.751 | deleterious | None | None | None | None | N |
| A/N | 0.9266 | likely_pathogenic | 0.9486 | pathogenic | -1.735 | Destabilizing | 0.447 | N | 0.739 | deleterious | None | None | None | None | N |
| A/P | 0.8906 | likely_pathogenic | 0.93 | pathogenic | -0.594 | Destabilizing | 0.896 | D | 0.739 | deleterious | N | 0.399290708 | None | None | N |
| A/Q | 0.9635 | likely_pathogenic | 0.9725 | pathogenic | -1.816 | Destabilizing | 0.85 | D | 0.757 | deleterious | None | None | None | None | N |
| A/R | 0.9761 | likely_pathogenic | 0.9862 | pathogenic | -1.253 | Destabilizing | 0.85 | D | 0.733 | deleterious | None | None | None | None | N |
| A/S | 0.1723 | likely_benign | 0.1606 | benign | -2.008 | Highly Destabilizing | 0.007 | N | 0.161 | neutral | N | 0.355074412 | None | None | N |
| A/T | 0.1518 | likely_benign | 0.1711 | benign | -1.844 | Destabilizing | 0.002 | N | 0.184 | neutral | N | 0.354572725 | None | None | N |
| A/V | 0.245 | likely_benign | 0.3381 | benign | -0.594 | Destabilizing | 0.379 | N | 0.643 | neutral | N | 0.343861674 | None | None | N |
| A/W | 0.995 | likely_pathogenic | 0.9968 | pathogenic | -1.597 | Destabilizing | 0.992 | D | 0.836 | deleterious | None | None | None | None | N |
| A/Y | 0.982 | likely_pathogenic | 0.9895 | pathogenic | -1.155 | Destabilizing | 0.972 | D | 0.795 | 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.