Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31429 | 94510;94511;94512 | chr2:178547240;178547239;178547238 | chr2:179411967;179411966;179411965 |
| N2AB | 29788 | 89587;89588;89589 | chr2:178547240;178547239;178547238 | chr2:179411967;179411966;179411965 |
| N2A | 28861 | 86806;86807;86808 | chr2:178547240;178547239;178547238 | chr2:179411967;179411966;179411965 |
| N2B | 22364 | 67315;67316;67317 | chr2:178547240;178547239;178547238 | chr2:179411967;179411966;179411965 |
| Novex-1 | 22489 | 67690;67691;67692 | chr2:178547240;178547239;178547238 | chr2:179411967;179411966;179411965 |
| Novex-2 | 22556 | 67891;67892;67893 | chr2:178547240;178547239;178547238 | chr2:179411967;179411966;179411965 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | None | None | 1.0 | D | 0.844 | 0.772 | 0.887746986894 | gnomAD-4.0.0 | 1.59132E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85858E-06 | 0 | 0 |
| W/R | None | -1.936 | 1.0 | D | 0.913 | 0.861 | 0.906553756881 |
Evila (2016) 
| None |
TMD 
|
comp het with R21209* | None | None | N | Genetic analysis of genes in 10 TMD families; co-segregation in 2-generation family (recessive inheritance, n = 3, 1 affected (total 5; disease state only where compound heterozygous for both W31429R and R21209*)); variant prioritisation; comp het with R21209* | None | None | None | None | None | None | None | None | None | None | None |
| W/R | None | -1.936 | 1.0 | D | 0.913 | 0.861 | 0.906553756881 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 1.01626E-03 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -3.864 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| W/C | 0.9989 | likely_pathogenic | 0.9991 | pathogenic | -2.006 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | D | 0.660916925 | None | None | N |
| W/D | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.826 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | None | None | None | None | N |
| W/E | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -3.74 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | None | None | None | None | N |
| W/F | 0.8517 | likely_pathogenic | 0.8401 | pathogenic | -2.437 | Highly Destabilizing | 1.0 | D | 0.898 | deleterious | None | None | None | None | N |
| W/G | 0.9905 | likely_pathogenic | 0.992 | pathogenic | -4.054 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.660916925 | None | None | N |
| W/H | 0.9988 | likely_pathogenic | 0.9989 | pathogenic | -2.755 | Highly Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| W/I | 0.9977 | likely_pathogenic | 0.9982 | pathogenic | -3.093 | Highly Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| W/K | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -2.672 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| W/L | 0.9927 | likely_pathogenic | 0.9938 | pathogenic | -3.093 | Highly Destabilizing | 1.0 | D | 0.859 | deleterious | D | 0.659907903 | None | None | N |
| W/M | 0.9973 | likely_pathogenic | 0.9978 | pathogenic | -2.424 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| W/N | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.194 | Highly Destabilizing | 1.0 | D | 0.924 | deleterious | None | None | None | None | N |
| W/P | 0.9999 | likely_pathogenic | 0.9999 | pathogenic | -3.38 | Highly Destabilizing | 1.0 | D | 0.927 | deleterious | None | None | None | None | N |
| W/Q | 0.9998 | likely_pathogenic | 0.9999 | pathogenic | -3.18 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| W/R | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -2.074 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | D | 0.660916925 | None | None | N |
| W/S | 0.998 | likely_pathogenic | 0.9985 | pathogenic | -3.388 | Highly Destabilizing | 1.0 | D | 0.892 | deleterious | D | 0.644665399 | None | None | N |
| W/T | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -3.242 | Highly Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| W/V | 0.9975 | likely_pathogenic | 0.9981 | pathogenic | -3.38 | Highly Destabilizing | 1.0 | D | 0.886 | deleterious | None | None | None | None | N |
| W/Y | 0.9682 | likely_pathogenic | 0.9698 | pathogenic | -2.31 | Highly Destabilizing | 1.0 | D | 0.851 | 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.