Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27748 | 83467;83468;83469 | chr2:178562890;178562889;178562888 | chr2:179427617;179427616;179427615 |
| N2AB | 26107 | 78544;78545;78546 | chr2:178562890;178562889;178562888 | chr2:179427617;179427616;179427615 |
| N2A | 25180 | 75763;75764;75765 | chr2:178562890;178562889;178562888 | chr2:179427617;179427616;179427615 |
| N2B | 18683 | 56272;56273;56274 | chr2:178562890;178562889;178562888 | chr2:179427617;179427616;179427615 |
| Novex-1 | 18808 | 56647;56648;56649 | chr2:178562890;178562889;178562888 | chr2:179427617;179427616;179427615 |
| Novex-2 | 18875 | 56848;56849;56850 | chr2:178562890;178562889;178562888 | chr2:179427617;179427616;179427615 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | rs760072489  |
-3.053 | 1.0 | N | 0.872 | 0.562 | 0.84047817739 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/S | rs760072489 |
-3.053 | 1.0 | N | 0.872 | 0.562 | 0.84047817739 | gnomAD-4.0.0 | 2.05315E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47834E-05 | 0 |
| L/V | None | None | 0.999 | N | 0.544 | 0.23 | 0.290962096972 | gnomAD-4.0.0 | 1.59219E-06 | None | None | None | None | N | None | 0 | 2.28854E-05 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.5057 | ambiguous | 0.4649 | ambiguous | -2.195 | Highly Destabilizing | 0.999 | D | 0.724 | prob.delet. | None | None | None | None | N |
| L/C | 0.8284 | likely_pathogenic | 0.8071 | pathogenic | -1.786 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| L/D | 0.9996 | likely_pathogenic | 0.9996 | pathogenic | -2.237 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| L/E | 0.9957 | likely_pathogenic | 0.9958 | pathogenic | -2.164 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/F | 0.922 | likely_pathogenic | 0.9098 | pathogenic | -1.575 | Destabilizing | 1.0 | D | 0.83 | deleterious | D | 0.522586083 | None | None | N |
| L/G | 0.9703 | likely_pathogenic | 0.9658 | pathogenic | -2.603 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| L/H | 0.9955 | likely_pathogenic | 0.9954 | pathogenic | -1.92 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| L/I | 0.1248 | likely_benign | 0.1199 | benign | -1.094 | Destabilizing | 0.999 | D | 0.537 | neutral | N | 0.489516624 | None | None | N |
| L/K | 0.9951 | likely_pathogenic | 0.9956 | pathogenic | -1.637 | Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| L/M | 0.3512 | ambiguous | 0.3343 | benign | -1.024 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| L/N | 0.9966 | likely_pathogenic | 0.9962 | pathogenic | -1.645 | Destabilizing | 1.0 | D | 0.88 | deleterious | None | None | None | None | N |
| L/P | 0.9959 | likely_pathogenic | 0.9967 | pathogenic | -1.434 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| L/Q | 0.9824 | likely_pathogenic | 0.9826 | pathogenic | -1.768 | Destabilizing | 1.0 | D | 0.885 | deleterious | None | None | None | None | N |
| L/R | 0.9866 | likely_pathogenic | 0.9881 | pathogenic | -1.103 | Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| L/S | 0.9553 | likely_pathogenic | 0.9456 | pathogenic | -2.304 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | N | 0.495834547 | None | None | N |
| L/T | 0.784 | likely_pathogenic | 0.7687 | pathogenic | -2.102 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| L/V | 0.0962 | likely_benign | 0.0948 | benign | -1.434 | Destabilizing | 0.999 | D | 0.544 | neutral | N | 0.445874916 | None | None | N |
| L/W | 0.9934 | likely_pathogenic | 0.9936 | pathogenic | -1.753 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | N |
| L/Y | 0.9943 | likely_pathogenic | 0.994 | pathogenic | -1.503 | Destabilizing | 1.0 | D | 0.876 | 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.