Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32818 | 98677;98678;98679 | chr2:178539613;178539612;178539611 | chr2:179404340;179404339;179404338 |
| N2AB | 31177 | 93754;93755;93756 | chr2:178539613;178539612;178539611 | chr2:179404340;179404339;179404338 |
| N2A | 30250 | 90973;90974;90975 | chr2:178539613;178539612;178539611 | chr2:179404340;179404339;179404338 |
| N2B | 23753 | 71482;71483;71484 | chr2:178539613;178539612;178539611 | chr2:179404340;179404339;179404338 |
| Novex-1 | 23878 | 71857;71858;71859 | chr2:178539613;178539612;178539611 | chr2:179404340;179404339;179404338 |
| Novex-2 | 23945 | 72058;72059;72060 | chr2:178539613;178539612;178539611 | chr2:179404340;179404339;179404338 |
| 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/K | rs794729551  |
-0.187 | 0.011 | N | 0.21 | 0.121 | 0.151104730317 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| R/K | rs794729551 |
-0.187 | 0.011 | N | 0.21 | 0.121 | 0.151104730317 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| R/K | rs794729551 |
-0.187 | 0.011 | N | 0.21 | 0.121 | 0.151104730317 | gnomAD-4.0.0 | 5.12407E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57171E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4586 | ambiguous | 0.5589 | ambiguous | -0.385 | Destabilizing | 0.919 | D | 0.614 | neutral | None | None | None | None | N |
| R/C | 0.2305 | likely_benign | 0.2734 | benign | -0.298 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| R/D | 0.7124 | likely_pathogenic | 0.7894 | pathogenic | 0.02 | Stabilizing | 0.976 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/E | 0.4087 | ambiguous | 0.4885 | ambiguous | 0.125 | Stabilizing | 0.851 | D | 0.553 | neutral | None | None | None | None | N |
| R/F | 0.6064 | likely_pathogenic | 0.6879 | pathogenic | -0.309 | Destabilizing | 0.996 | D | 0.736 | prob.delet. | None | None | None | None | N |
| R/G | 0.3376 | likely_benign | 0.4089 | ambiguous | -0.672 | Destabilizing | 0.896 | D | 0.642 | neutral | N | 0.475056099 | None | None | N |
| R/H | 0.1227 | likely_benign | 0.1421 | benign | -1.109 | Destabilizing | 0.996 | D | 0.627 | neutral | None | None | None | None | N |
| R/I | 0.2921 | likely_benign | 0.3655 | ambiguous | 0.368 | Stabilizing | 0.984 | D | 0.741 | deleterious | N | 0.456200979 | None | None | N |
| R/K | 0.0929 | likely_benign | 0.1076 | benign | -0.426 | Destabilizing | 0.011 | N | 0.21 | neutral | N | 0.350878881 | None | None | N |
| R/L | 0.2177 | likely_benign | 0.2787 | benign | 0.368 | Stabilizing | 0.919 | D | 0.642 | neutral | None | None | None | None | N |
| R/M | 0.2863 | likely_benign | 0.3669 | ambiguous | None | Stabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | N |
| R/N | 0.5237 | ambiguous | 0.6253 | pathogenic | 0.081 | Stabilizing | 0.976 | D | 0.621 | neutral | None | None | None | None | N |
| R/P | 0.8882 | likely_pathogenic | 0.9066 | pathogenic | 0.139 | Stabilizing | 0.988 | D | 0.748 | deleterious | None | None | None | None | N |
| R/Q | 0.1097 | likely_benign | 0.1299 | benign | -0.072 | Destabilizing | 0.976 | D | 0.635 | neutral | None | None | None | None | N |
| R/S | 0.515 | ambiguous | 0.6106 | pathogenic | -0.521 | Destabilizing | 0.896 | D | 0.647 | neutral | N | 0.427491438 | None | None | N |
| R/T | 0.3339 | likely_benign | 0.4228 | ambiguous | -0.248 | Destabilizing | 0.896 | D | 0.667 | neutral | N | 0.417506518 | None | None | N |
| R/V | 0.3991 | ambiguous | 0.4753 | ambiguous | 0.139 | Stabilizing | 0.988 | D | 0.726 | prob.delet. | None | None | None | None | N |
| R/W | 0.2932 | likely_benign | 0.3411 | ambiguous | -0.099 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/Y | 0.4497 | ambiguous | 0.519 | ambiguous | 0.229 | Stabilizing | 0.996 | D | 0.744 | 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.