Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18060 | 54403;54404;54405 | chr2:178604999;178604998;178604997 | chr2:179469726;179469725;179469724 |
| N2AB | 16419 | 49480;49481;49482 | chr2:178604999;178604998;178604997 | chr2:179469726;179469725;179469724 |
| N2A | 15492 | 46699;46700;46701 | chr2:178604999;178604998;178604997 | chr2:179469726;179469725;179469724 |
| N2B | 8995 | 27208;27209;27210 | chr2:178604999;178604998;178604997 | chr2:179469726;179469725;179469724 |
| Novex-1 | 9120 | 27583;27584;27585 | chr2:178604999;178604998;178604997 | chr2:179469726;179469725;179469724 |
| Novex-2 | 9187 | 27784;27785;27786 | chr2:178604999;178604998;178604997 | chr2:179469726;179469725;179469724 |
| 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 | rs778548912  |
-2.484 | 0.058 | N | 0.33 | 0.387 | 0.513394077459 | gnomAD-2.1.1 | 1.69E-05 | None | None | None | None | N | None | 0 | 8.95E-05 | None | 0 | 0 | None | 0 | None | 0 | 9.27E-06 | 0 |
| V/A | rs778548912 |
-2.484 | 0.058 | N | 0.33 | 0.387 | 0.513394077459 | gnomAD-4.0.0 | 4.15284E-06 | None | None | None | None | N | None | 0 | 6.87411E-05 | None | 0 | 0 | None | 0 | 0 | 1.81437E-06 | 0 | 1.67819E-05 |
| V/I | rs190574498 |
-0.524 | 0.843 | N | 0.599 | 0.115 | None | gnomAD-2.1.1 | 7.46E-05 | None | None | None | None | N | None | 1.66362E-04 | 2.91E-05 | None | 0 | 0 | None | 3.63E-05 | None | 1.25063E-04 | 8.12E-05 | 1.47449E-04 |
| V/I | rs190574498 |
-0.524 | 0.843 | N | 0.599 | 0.115 | None | gnomAD-3.1.2 | 5.27E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.83E-05 | 0 | 0 |
| V/I | rs190574498 |
-0.524 | 0.843 | N | 0.599 | 0.115 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/I | rs190574498 |
-0.524 | 0.843 | N | 0.599 | 0.115 | None | gnomAD-4.0.0 | 4.50983E-05 | None | None | None | None | N | None | 4.02966E-05 | 1.69999E-05 | None | 0 | 0 | None | 2.37049E-04 | 0 | 4.27344E-05 | 3.39643E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8971 | likely_pathogenic | 0.8723 | pathogenic | -2.561 | Highly Destabilizing | 0.058 | N | 0.33 | neutral | N | 0.500733078 | None | None | N |
| V/C | 0.9543 | likely_pathogenic | 0.9501 | pathogenic | -2.124 | Highly Destabilizing | 0.998 | D | 0.77 | deleterious | None | None | None | None | N |
| V/D | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -3.452 | Highly Destabilizing | 0.971 | D | 0.867 | deleterious | N | 0.512596362 | None | None | N |
| V/E | 0.9971 | likely_pathogenic | 0.9962 | pathogenic | -3.205 | Highly Destabilizing | 0.978 | D | 0.845 | deleterious | None | None | None | None | N |
| V/F | 0.7867 | likely_pathogenic | 0.7657 | pathogenic | -1.501 | Destabilizing | 0.954 | D | 0.791 | deleterious | N | 0.488451719 | None | None | N |
| V/G | 0.9705 | likely_pathogenic | 0.9617 | pathogenic | -3.123 | Highly Destabilizing | 0.942 | D | 0.837 | deleterious | N | 0.512596362 | None | None | N |
| V/H | 0.9986 | likely_pathogenic | 0.9981 | pathogenic | -2.852 | Highly Destabilizing | 0.998 | D | 0.845 | deleterious | None | None | None | None | N |
| V/I | 0.0874 | likely_benign | 0.0891 | benign | -0.957 | Destabilizing | 0.843 | D | 0.599 | neutral | N | 0.510795107 | None | None | N |
| V/K | 0.9972 | likely_pathogenic | 0.9962 | pathogenic | -2.271 | Highly Destabilizing | 0.978 | D | 0.851 | deleterious | None | None | None | None | N |
| V/L | 0.4544 | ambiguous | 0.4324 | ambiguous | -0.957 | Destabilizing | 0.036 | N | 0.3 | neutral | N | 0.437934065 | None | None | N |
| V/M | 0.593 | likely_pathogenic | 0.5686 | pathogenic | -1.013 | Destabilizing | 0.956 | D | 0.725 | prob.delet. | None | None | None | None | N |
| V/N | 0.9965 | likely_pathogenic | 0.9957 | pathogenic | -2.701 | Highly Destabilizing | 0.993 | D | 0.841 | deleterious | None | None | None | None | N |
| V/P | 0.9978 | likely_pathogenic | 0.9972 | pathogenic | -1.469 | Destabilizing | 0.978 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Q | 0.9954 | likely_pathogenic | 0.9938 | pathogenic | -2.499 | Highly Destabilizing | 0.993 | D | 0.813 | deleterious | None | None | None | None | N |
| V/R | 0.9943 | likely_pathogenic | 0.9924 | pathogenic | -2.041 | Highly Destabilizing | 0.978 | D | 0.856 | deleterious | None | None | None | None | N |
| V/S | 0.9856 | likely_pathogenic | 0.9822 | pathogenic | -3.288 | Highly Destabilizing | 0.915 | D | 0.828 | deleterious | None | None | None | None | N |
| V/T | 0.9079 | likely_pathogenic | 0.8931 | pathogenic | -2.902 | Highly Destabilizing | 0.86 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/W | 0.9974 | likely_pathogenic | 0.9964 | pathogenic | -2.1 | Highly Destabilizing | 0.998 | D | 0.838 | deleterious | None | None | None | None | N |
| V/Y | 0.9903 | likely_pathogenic | 0.9878 | pathogenic | -1.79 | Destabilizing | 0.978 | D | 0.768 | 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.