Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15104 | 45535;45536;45537 | chr2:178621514;178621513;178621512 | chr2:179486241;179486240;179486239 |
| N2AB | 13463 | 40612;40613;40614 | chr2:178621514;178621513;178621512 | chr2:179486241;179486240;179486239 |
| N2A | 12536 | 37831;37832;37833 | chr2:178621514;178621513;178621512 | chr2:179486241;179486240;179486239 |
| N2B | 6039 | 18340;18341;18342 | chr2:178621514;178621513;178621512 | chr2:179486241;179486240;179486239 |
| Novex-1 | 6164 | 18715;18716;18717 | chr2:178621514;178621513;178621512 | chr2:179486241;179486240;179486239 |
| Novex-2 | 6231 | 18916;18917;18918 | chr2:178621514;178621513;178621512 | chr2:179486241;179486240;179486239 |
| 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/F | rs370782950  |
-1.923 | 1.0 | D | 0.773 | 0.422 | None | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| L/F | rs370782950 |
-1.923 | 1.0 | D | 0.773 | 0.422 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.95E-05 | 0 | 0 |
| L/F | rs370782950 |
-1.923 | 1.0 | D | 0.773 | 0.422 | None | gnomAD-4.0.0 | 4.34152E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.9368E-06 | 0 | 0 |
| L/P | rs778421383 |
-1.749 | 1.0 | N | 0.825 | 0.653 | 0.881115435736 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| L/P | rs778421383 |
-1.749 | 1.0 | N | 0.825 | 0.653 | 0.881115435736 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/P | rs778421383 |
-1.749 | 1.0 | N | 0.825 | 0.653 | 0.881115435736 | gnomAD-4.0.0 | 1.86075E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5444E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.8813 | likely_pathogenic | 0.8424 | pathogenic | -2.107 | Highly Destabilizing | 0.999 | D | 0.73 | prob.delet. | None | None | None | None | N |
| L/C | 0.9406 | likely_pathogenic | 0.918 | pathogenic | -1.33 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| L/D | 0.9935 | likely_pathogenic | 0.9899 | pathogenic | -1.9 | Destabilizing | 1.0 | D | 0.834 | deleterious | None | None | None | None | N |
| L/E | 0.9746 | likely_pathogenic | 0.9611 | pathogenic | -1.751 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/F | 0.6224 | likely_pathogenic | 0.6922 | pathogenic | -1.247 | Destabilizing | 1.0 | D | 0.773 | deleterious | D | 0.530215558 | None | None | N |
| L/G | 0.9603 | likely_pathogenic | 0.9492 | pathogenic | -2.589 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/H | 0.9117 | likely_pathogenic | 0.8611 | pathogenic | -1.983 | Destabilizing | 1.0 | D | 0.821 | deleterious | D | 0.646246291 | None | None | N |
| L/I | 0.2689 | likely_benign | 0.2175 | benign | -0.765 | Destabilizing | 0.999 | D | 0.558 | neutral | N | 0.50721147 | None | None | N |
| L/K | 0.9315 | likely_pathogenic | 0.9105 | pathogenic | -1.464 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| L/M | 0.3509 | ambiguous | 0.2976 | benign | -0.666 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| L/N | 0.9568 | likely_pathogenic | 0.9318 | pathogenic | -1.557 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| L/P | 0.9866 | likely_pathogenic | 0.9746 | pathogenic | -1.187 | Destabilizing | 1.0 | D | 0.825 | deleterious | N | 0.506955764 | None | None | N |
| L/Q | 0.8978 | likely_pathogenic | 0.8459 | pathogenic | -1.527 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/R | 0.9136 | likely_pathogenic | 0.8833 | pathogenic | -1.124 | Destabilizing | 1.0 | D | 0.828 | deleterious | D | 0.605842024 | None | None | N |
| L/S | 0.9358 | likely_pathogenic | 0.897 | pathogenic | -2.273 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| L/T | 0.8302 | likely_pathogenic | 0.7881 | pathogenic | -1.987 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| L/V | 0.3627 | ambiguous | 0.3107 | benign | -1.187 | Destabilizing | 0.999 | D | 0.572 | neutral | N | 0.477636127 | None | None | N |
| L/W | 0.9416 | likely_pathogenic | 0.9017 | pathogenic | -1.543 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| L/Y | 0.9313 | likely_pathogenic | 0.8988 | pathogenic | -1.241 | Destabilizing | 1.0 | D | 0.827 | 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.