Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29429 | 88510;88511;88512 | chr2:178556869;178556868;178556867 | chr2:179421596;179421595;179421594 |
| N2AB | 27788 | 83587;83588;83589 | chr2:178556869;178556868;178556867 | chr2:179421596;179421595;179421594 |
| N2A | 26861 | 80806;80807;80808 | chr2:178556869;178556868;178556867 | chr2:179421596;179421595;179421594 |
| N2B | 20364 | 61315;61316;61317 | chr2:178556869;178556868;178556867 | chr2:179421596;179421595;179421594 |
| Novex-1 | 20489 | 61690;61691;61692 | chr2:178556869;178556868;178556867 | chr2:179421596;179421595;179421594 |
| Novex-2 | 20556 | 61891;61892;61893 | chr2:178556869;178556868;178556867 | chr2:179421596;179421595;179421594 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs373738818  |
-1.168 | None | N | 0.188 | 0.07 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | N | None | 4.13E-05 | 0 | None | 0 | 0 | None | 0 | None | 4.01E-05 | 1.09519E-04 | 0 |
| I/V | rs373738818 |
-1.168 | None | N | 0.188 | 0.07 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 1.76372E-04 | 0 | 0 |
| I/V | rs373738818 |
-1.168 | None | N | 0.188 | 0.07 | None | gnomAD-4.0.0 | 1.23326E-04 | None | None | None | None | N | None | 1.33437E-05 | 0 | None | 0 | 0 | None | 3.12999E-05 | 0 | 1.54261E-04 | 0 | 2.24143E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.406 | ambiguous | 0.3162 | benign | -2.28 | Highly Destabilizing | 0.002 | N | 0.423 | neutral | None | None | None | None | N |
| I/C | 0.6992 | likely_pathogenic | 0.6338 | pathogenic | -1.563 | Destabilizing | 0.676 | D | 0.667 | prob.neutral | None | None | None | None | N |
| I/D | 0.9206 | likely_pathogenic | 0.8781 | pathogenic | -2.291 | Highly Destabilizing | 0.676 | D | 0.749 | deleterious | None | None | None | None | N |
| I/E | 0.7972 | likely_pathogenic | 0.7373 | pathogenic | -2.087 | Highly Destabilizing | 0.373 | N | 0.733 | deleterious | None | None | None | None | N |
| I/F | 0.2836 | likely_benign | 0.2202 | benign | -1.337 | Destabilizing | 0.437 | N | 0.687 | prob.delet. | N | 0.461715594 | None | None | N |
| I/G | 0.8057 | likely_pathogenic | 0.7277 | pathogenic | -2.795 | Highly Destabilizing | 0.227 | N | 0.683 | prob.neutral | None | None | None | None | N |
| I/H | 0.7438 | likely_pathogenic | 0.6712 | pathogenic | -2.023 | Highly Destabilizing | 0.96 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/K | 0.6238 | likely_pathogenic | 0.5584 | ambiguous | -1.8 | Destabilizing | 0.676 | D | 0.735 | deleterious | None | None | None | None | N |
| I/L | 0.1605 | likely_benign | 0.1354 | benign | -0.816 | Destabilizing | 0.02 | N | 0.455 | neutral | N | 0.503786203 | None | None | N |
| I/M | 0.141 | likely_benign | 0.1184 | benign | -0.723 | Destabilizing | 0.437 | N | 0.625 | neutral | N | 0.480073338 | None | None | N |
| I/N | 0.5573 | ambiguous | 0.4656 | ambiguous | -2.097 | Highly Destabilizing | 0.828 | D | 0.753 | deleterious | N | 0.491847718 | None | None | N |
| I/P | 0.9691 | likely_pathogenic | 0.9512 | pathogenic | -1.282 | Destabilizing | 0.676 | D | 0.747 | deleterious | None | None | None | None | N |
| I/Q | 0.6431 | likely_pathogenic | 0.5723 | pathogenic | -1.991 | Destabilizing | 0.864 | D | 0.752 | deleterious | None | None | None | None | N |
| I/R | 0.5477 | ambiguous | 0.476 | ambiguous | -1.461 | Destabilizing | 0.676 | D | 0.751 | deleterious | None | None | None | None | N |
| I/S | 0.5185 | ambiguous | 0.4252 | ambiguous | -2.803 | Highly Destabilizing | 0.1 | N | 0.653 | prob.neutral | N | 0.49032678 | None | None | N |
| I/T | 0.3256 | likely_benign | 0.2617 | benign | -2.445 | Highly Destabilizing | 0.181 | N | 0.675 | prob.neutral | N | 0.468420183 | None | None | N |
| I/V | 0.0537 | likely_benign | 0.053 | benign | -1.282 | Destabilizing | None | N | 0.188 | neutral | N | 0.449202357 | None | None | N |
| I/W | 0.9366 | likely_pathogenic | 0.9025 | pathogenic | -1.621 | Destabilizing | 0.96 | D | 0.753 | deleterious | None | None | None | None | N |
| I/Y | 0.6949 | likely_pathogenic | 0.6138 | pathogenic | -1.325 | Destabilizing | 0.676 | D | 0.743 | 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.