Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25893 | 77902;77903;77904 | chr2:178568455;178568454;178568453 | chr2:179433182;179433181;179433180 |
| N2AB | 24252 | 72979;72980;72981 | chr2:178568455;178568454;178568453 | chr2:179433182;179433181;179433180 |
| N2A | 23325 | 70198;70199;70200 | chr2:178568455;178568454;178568453 | chr2:179433182;179433181;179433180 |
| N2B | 16828 | 50707;50708;50709 | chr2:178568455;178568454;178568453 | chr2:179433182;179433181;179433180 |
| Novex-1 | 16953 | 51082;51083;51084 | chr2:178568455;178568454;178568453 | chr2:179433182;179433181;179433180 |
| Novex-2 | 17020 | 51283;51284;51285 | chr2:178568455;178568454;178568453 | chr2:179433182;179433181;179433180 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | None | None | 1.0 | D | 0.901 | 0.489 | 0.675998447366 | gnomAD-4.0.0 | 2.0532E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69884E-06 | 0 | 0 |
| P/R | None | None | 1.0 | N | 0.907 | 0.474 | 0.546131560702 | gnomAD-4.0.0 | 6.84399E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99612E-07 | 0 | 0 |
| P/S | rs1462410139  |
-2.027 | 1.0 | N | 0.852 | 0.447 | 0.430579932962 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 1.45197E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1462410139 |
-2.027 | 1.0 | N | 0.852 | 0.447 | 0.430579932962 | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | I | None | 0 | 9.18153E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1462410139 |
-2.027 | 1.0 | N | 0.852 | 0.447 | 0.430579932962 | gnomAD-4.0.0 | 2.43573E-05 | None | None | None | None | I | None | 0 | 3.22318E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0621 | likely_benign | 0.0827 | benign | -1.851 | Destabilizing | 1.0 | D | 0.849 | deleterious | N | 0.496831306 | None | None | I |
| P/C | 0.4202 | ambiguous | 0.5251 | ambiguous | -1.203 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| P/D | 0.8575 | likely_pathogenic | 0.9111 | pathogenic | -2.206 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| P/E | 0.4461 | ambiguous | 0.5601 | ambiguous | -2.165 | Highly Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| P/F | 0.5857 | likely_pathogenic | 0.6955 | pathogenic | -1.349 | Destabilizing | 1.0 | D | 0.908 | deleterious | None | None | None | None | I |
| P/G | 0.5302 | ambiguous | 0.6387 | pathogenic | -2.212 | Highly Destabilizing | 1.0 | D | 0.903 | deleterious | None | None | None | None | I |
| P/H | 0.3388 | likely_benign | 0.45 | ambiguous | -1.798 | Destabilizing | 1.0 | D | 0.891 | deleterious | N | 0.518305398 | None | None | I |
| P/I | 0.2073 | likely_benign | 0.2562 | benign | -0.922 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | I |
| P/K | 0.3005 | likely_benign | 0.3904 | ambiguous | -1.503 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| P/L | 0.1529 | likely_benign | 0.206 | benign | -0.922 | Destabilizing | 1.0 | D | 0.901 | deleterious | D | 0.524799858 | None | None | I |
| P/M | 0.2884 | likely_benign | 0.3703 | ambiguous | -0.676 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| P/N | 0.6682 | likely_pathogenic | 0.7661 | pathogenic | -1.381 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | I |
| P/Q | 0.1885 | likely_benign | 0.2512 | benign | -1.53 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | I |
| P/R | 0.2134 | likely_benign | 0.2744 | benign | -0.995 | Destabilizing | 1.0 | D | 0.907 | deleterious | N | 0.516784461 | None | None | I |
| P/S | 0.2007 | likely_benign | 0.2787 | benign | -1.879 | Destabilizing | 1.0 | D | 0.852 | deleterious | N | 0.499894747 | None | None | I |
| P/T | 0.1426 | likely_benign | 0.198 | benign | -1.738 | Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.503555278 | None | None | I |
| P/V | 0.147 | likely_benign | 0.1809 | benign | -1.201 | Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | I |
| P/W | 0.8645 | likely_pathogenic | 0.9094 | pathogenic | -1.644 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | I |
| P/Y | 0.6052 | likely_pathogenic | 0.7194 | pathogenic | -1.369 | Destabilizing | 1.0 | D | 0.917 | deleterious | None | None | None | None | I |
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.