Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31781 | 95566;95567;95568 | chr2:178545895;178545894;178545893 | chr2:179410622;179410621;179410620 |
| N2AB | 30140 | 90643;90644;90645 | chr2:178545895;178545894;178545893 | chr2:179410622;179410621;179410620 |
| N2A | 29213 | 87862;87863;87864 | chr2:178545895;178545894;178545893 | chr2:179410622;179410621;179410620 |
| N2B | 22716 | 68371;68372;68373 | chr2:178545895;178545894;178545893 | chr2:179410622;179410621;179410620 |
| Novex-1 | 22841 | 68746;68747;68748 | chr2:178545895;178545894;178545893 | chr2:179410622;179410621;179410620 |
| Novex-2 | 22908 | 68947;68948;68949 | chr2:178545895;178545894;178545893 | chr2:179410622;179410621;179410620 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | rs748984928  |
-1.236 | 1.0 | D | 0.737 | 0.727 | 0.765735979443 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/L | rs748984928 |
-1.236 | 1.0 | D | 0.737 | 0.727 | 0.765735979443 | gnomAD-4.0.0 | 1.3684E-06 | None | None | None | None | I | None | 0 | 4.47227E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs748984928 |
None | 1.0 | D | 0.819 | 0.694 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs748984928 |
None | 1.0 | D | 0.819 | 0.694 | None | gnomAD-4.0.0 | 6.57134E-06 | None | None | None | None | I | None | 2.41313E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | None | -1.259 | 1.0 | N | 0.787 | 0.562 | 0.435915822735 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 6.46E-05 | 5.8E-05 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| R/Q | None | -1.259 | 1.0 | N | 0.787 | 0.562 | 0.435915822735 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.06954E-04 | 0 |
| R/Q | None | -1.259 | 1.0 | N | 0.787 | 0.562 | 0.435915822735 | gnomAD-4.0.0 | 1.36329E-05 | None | None | None | None | I | None | 8.00983E-05 | 3.33411E-05 | None | 0 | 2.22826E-05 | None | 0 | 0 | 9.32361E-06 | 1.09784E-05 | 1.60108E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.963 | likely_pathogenic | 0.975 | pathogenic | -1.918 | Destabilizing | 0.999 | D | 0.64 | neutral | None | None | None | None | I |
| R/C | 0.5684 | likely_pathogenic | 0.6345 | pathogenic | -1.821 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| R/D | 0.9969 | likely_pathogenic | 0.9981 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| R/E | 0.9633 | likely_pathogenic | 0.9723 | pathogenic | -0.992 | Destabilizing | 0.999 | D | 0.688 | prob.neutral | None | None | None | None | I |
| R/F | 0.9882 | likely_pathogenic | 0.9902 | pathogenic | -0.927 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | I |
| R/G | 0.9425 | likely_pathogenic | 0.9658 | pathogenic | -2.218 | Highly Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.565505046 | None | None | I |
| R/H | 0.4967 | ambiguous | 0.5121 | ambiguous | -2.169 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| R/I | 0.9569 | likely_pathogenic | 0.9652 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | I |
| R/K | 0.5664 | likely_pathogenic | 0.5592 | ambiguous | -1.406 | Destabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | I |
| R/L | 0.9188 | likely_pathogenic | 0.9301 | pathogenic | -1.036 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.527904184 | None | None | I |
| R/M | 0.9555 | likely_pathogenic | 0.9651 | pathogenic | -1.594 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| R/N | 0.9879 | likely_pathogenic | 0.991 | pathogenic | -1.508 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | I |
| R/P | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -1.322 | Destabilizing | 1.0 | D | 0.819 | deleterious | D | 0.566012025 | None | None | I |
| R/Q | 0.4266 | ambiguous | 0.4907 | ambiguous | -1.194 | Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.507518524 | None | None | I |
| R/S | 0.9716 | likely_pathogenic | 0.9809 | pathogenic | -2.163 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/T | 0.9623 | likely_pathogenic | 0.9746 | pathogenic | -1.773 | Destabilizing | 1.0 | D | 0.74 | deleterious | None | None | None | None | I |
| R/V | 0.9595 | likely_pathogenic | 0.9692 | pathogenic | -1.322 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| R/W | 0.8312 | likely_pathogenic | 0.8605 | pathogenic | -0.631 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| R/Y | 0.9586 | likely_pathogenic | 0.9672 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.848 | 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.