Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19219 | 57880;57881;57882 | chr2:178595699;178595698;178595697 | chr2:179460426;179460425;179460424 |
| N2AB | 17578 | 52957;52958;52959 | chr2:178595699;178595698;178595697 | chr2:179460426;179460425;179460424 |
| N2A | 16651 | 50176;50177;50178 | chr2:178595699;178595698;178595697 | chr2:179460426;179460425;179460424 |
| N2B | 10154 | 30685;30686;30687 | chr2:178595699;178595698;178595697 | chr2:179460426;179460425;179460424 |
| Novex-1 | 10279 | 31060;31061;31062 | chr2:178595699;178595698;178595697 | chr2:179460426;179460425;179460424 |
| Novex-2 | 10346 | 31261;31262;31263 | chr2:178595699;178595698;178595697 | chr2:179460426;179460425;179460424 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/F | rs201541213  |
-1.37 | 0.999 | D | 0.627 | 0.709 | None | gnomAD-2.1.1 | 1.50872E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.37941E-04 | None | 0 | 2.97926E-04 | 0 |
| Y/F | rs201541213 |
-1.37 | 0.999 | D | 0.627 | 0.709 | None | gnomAD-3.1.2 | 1.5128E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 3.08887E-04 | 2.07297E-04 | 0 |
| Y/F | rs201541213 |
-1.37 | 0.999 | D | 0.627 | 0.709 | None | gnomAD-4.0.0 | 3.51815E-04 | None | None | None | None | N | None | 4.00812E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.51729E-04 | 8.91285E-05 | 3.6911E-04 |
| Y/H | rs1220456349 |
-2.877 | 1.0 | D | 0.795 | 0.834 | 0.809015641971 | gnomAD-2.1.1 | 1.1E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.41E-05 | 0 |
| Y/H | rs1220456349 |
-2.877 | 1.0 | D | 0.795 | 0.834 | 0.809015641971 | 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 |
| Y/H | rs1220456349 |
-2.877 | 1.0 | D | 0.795 | 0.834 | 0.809015641971 | gnomAD-4.0.0 | 4.97221E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.79245E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9948 | likely_pathogenic | 0.9954 | pathogenic | -3.554 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| Y/C | 0.893 | likely_pathogenic | 0.9288 | pathogenic | -2.077 | Highly Destabilizing | 1.0 | D | 0.88 | deleterious | D | 0.639814968 | None | None | N |
| Y/D | 0.9958 | likely_pathogenic | 0.9962 | pathogenic | -3.916 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | D | 0.640016772 | None | None | N |
| Y/E | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -3.693 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| Y/F | 0.1669 | likely_benign | 0.18 | benign | -1.409 | Destabilizing | 0.999 | D | 0.627 | neutral | D | 0.551876362 | None | None | N |
| Y/G | 0.992 | likely_pathogenic | 0.9926 | pathogenic | -3.97 | Highly Destabilizing | 1.0 | D | 0.925 | deleterious | None | None | None | None | N |
| Y/H | 0.9612 | likely_pathogenic | 0.97 | pathogenic | -2.702 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.639411359 | None | None | N |
| Y/I | 0.9596 | likely_pathogenic | 0.9654 | pathogenic | -2.14 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| Y/K | 0.9986 | likely_pathogenic | 0.9986 | pathogenic | -2.52 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| Y/L | 0.9386 | likely_pathogenic | 0.9459 | pathogenic | -2.14 | Highly Destabilizing | 0.999 | D | 0.746 | deleterious | None | None | None | None | N |
| Y/M | 0.9761 | likely_pathogenic | 0.9795 | pathogenic | -1.93 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| Y/N | 0.9794 | likely_pathogenic | 0.9825 | pathogenic | -3.344 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | D | 0.639814968 | None | None | N |
| Y/P | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.633 | Highly Destabilizing | 1.0 | D | 0.942 | deleterious | None | None | None | None | N |
| Y/Q | 0.998 | likely_pathogenic | 0.9983 | pathogenic | -3.06 | Highly Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| Y/R | 0.994 | likely_pathogenic | 0.9947 | pathogenic | -2.319 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| Y/S | 0.9855 | likely_pathogenic | 0.9884 | pathogenic | -3.65 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.639814968 | None | None | N |
| Y/T | 0.992 | likely_pathogenic | 0.9931 | pathogenic | -3.303 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| Y/V | 0.9319 | likely_pathogenic | 0.9422 | pathogenic | -2.633 | Highly Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| Y/W | 0.82 | likely_pathogenic | 0.8484 | pathogenic | -0.623 | Destabilizing | 1.0 | D | 0.785 | 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.