Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2300 | 7123;7124;7125 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
| N2AB | 2300 | 7123;7124;7125 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
| N2A | 2300 | 7123;7124;7125 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
| N2B | 2254 | 6985;6986;6987 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
| Novex-1 | 2254 | 6985;6986;6987 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
| Novex-2 | 2254 | 6985;6986;6987 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
| Novex-3 | 2300 | 7123;7124;7125 | chr2:178774366;178774365;178774364 | chr2:179639093;179639092;179639091 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs772093035  |
-1.384 | 1.0 | N | 0.662 | 0.388 | 0.519675384768 | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.1E-05 | 0 |
| Y/C | rs772093035 |
-1.384 | 1.0 | N | 0.662 | 0.388 | 0.519675384768 | gnomAD-3.1.2 | 1.18231E-04 | None | None | None | None | N | None | 0 | 0 | 1.53509E-02 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| Y/C | rs772093035 |
-1.384 | 1.0 | N | 0.662 | 0.388 | 0.519675384768 | gnomAD-4.0.0 | 4.70868E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.91528E-05 | 1.09786E-05 | 4.80138E-05 |
| Y/F | rs772093035 |
-1.126 | 0.217 | N | 0.207 | 0.168 | 0.235664433957 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/F | rs772093035 |
-1.126 | 0.217 | N | 0.207 | 0.168 | 0.235664433957 | gnomAD-4.0.0 | 4.78862E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11538E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8821 | likely_pathogenic | 0.8895 | pathogenic | -2.961 | Highly Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | N |
| Y/C | 0.3217 | likely_benign | 0.3139 | benign | -1.427 | Destabilizing | 1.0 | D | 0.662 | neutral | N | 0.506370845 | None | None | N |
| Y/D | 0.8772 | likely_pathogenic | 0.884 | pathogenic | -2.214 | Highly Destabilizing | 0.999 | D | 0.711 | prob.delet. | D | 0.587212843 | None | None | N |
| Y/E | 0.9027 | likely_pathogenic | 0.91 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| Y/F | 0.0726 | likely_benign | 0.0727 | benign | -1.196 | Destabilizing | 0.217 | N | 0.207 | neutral | N | 0.443872049 | None | None | N |
| Y/G | 0.8409 | likely_pathogenic | 0.8515 | pathogenic | -3.313 | Highly Destabilizing | 1.0 | D | 0.704 | prob.neutral | None | None | None | None | N |
| Y/H | 0.32 | likely_benign | 0.3286 | benign | -1.594 | Destabilizing | 0.999 | D | 0.631 | neutral | D | 0.586033838 | None | None | N |
| Y/I | 0.6087 | likely_pathogenic | 0.6295 | pathogenic | -1.833 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| Y/K | 0.7822 | likely_pathogenic | 0.7915 | pathogenic | -1.59 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| Y/L | 0.5802 | likely_pathogenic | 0.5894 | pathogenic | -1.833 | Destabilizing | 0.983 | D | 0.571 | neutral | None | None | None | None | N |
| Y/M | 0.6653 | likely_pathogenic | 0.6844 | pathogenic | -1.477 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | N |
| Y/N | 0.5018 | ambiguous | 0.5177 | ambiguous | -1.994 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | D | 0.547174414 | None | None | N |
| Y/P | 0.9981 | likely_pathogenic | 0.9982 | pathogenic | -2.214 | Highly Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| Y/Q | 0.7325 | likely_pathogenic | 0.7426 | pathogenic | -1.943 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| Y/R | 0.6531 | likely_pathogenic | 0.6602 | pathogenic | -1.081 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| Y/S | 0.6071 | likely_pathogenic | 0.625 | pathogenic | -2.525 | Highly Destabilizing | 0.999 | D | 0.697 | prob.neutral | N | 0.46920605 | None | None | N |
| Y/T | 0.7868 | likely_pathogenic | 0.8026 | pathogenic | -2.294 | Highly Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| Y/V | 0.585 | likely_pathogenic | 0.6075 | pathogenic | -2.214 | Highly Destabilizing | 0.992 | D | 0.618 | neutral | None | None | None | None | N |
| Y/W | 0.5437 | ambiguous | 0.5544 | ambiguous | -0.546 | Destabilizing | 1.0 | D | 0.629 | neutral | 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.