Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16766 | 50521;50522;50523 | chr2:178612115;178612114;178612113 | chr2:179476842;179476841;179476840 |
| N2AB | 15125 | 45598;45599;45600 | chr2:178612115;178612114;178612113 | chr2:179476842;179476841;179476840 |
| N2A | 14198 | 42817;42818;42819 | chr2:178612115;178612114;178612113 | chr2:179476842;179476841;179476840 |
| N2B | 7701 | 23326;23327;23328 | chr2:178612115;178612114;178612113 | chr2:179476842;179476841;179476840 |
| Novex-1 | 7826 | 23701;23702;23703 | chr2:178612115;178612114;178612113 | chr2:179476842;179476841;179476840 |
| Novex-2 | 7893 | 23902;23903;23904 | chr2:178612115;178612114;178612113 | chr2:179476842;179476841;179476840 |
| 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/G | None | None | 0.004 | N | 0.165 | 0.237 | 0.229264304666 | gnomAD-4.0.0 | 6.84986E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.53872E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs747224934  |
-0.032 | 0.96 | N | 0.418 | 0.252 | 0.260735089382 | gnomAD-2.1.1 | 4.31E-05 | None | None | None | None | N | None | 1.65837E-04 | 5.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 4.72E-05 | 0 |
| R/Q | rs747224934 |
-0.032 | 0.96 | N | 0.418 | 0.252 | 0.260735089382 | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 2.17349E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| R/Q | rs747224934 |
-0.032 | 0.96 | N | 0.418 | 0.252 | 0.260735089382 | gnomAD-4.0.0 | 3.72243E-05 | None | None | None | None | N | None | 1.60424E-04 | 5.01404E-05 | None | 0 | 0 | None | 0 | 0 | 3.64724E-05 | 0 | 3.2077E-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 | 0.57 | likely_pathogenic | 0.6308 | pathogenic | 0.127 | Stabilizing | 0.25 | N | 0.409 | neutral | None | None | None | None | N |
| R/C | 0.4081 | ambiguous | 0.358 | ambiguous | 0.079 | Stabilizing | 0.992 | D | 0.391 | neutral | None | None | None | None | N |
| R/D | 0.7606 | likely_pathogenic | 0.804 | pathogenic | -0.126 | Destabilizing | 0.617 | D | 0.407 | neutral | None | None | None | None | N |
| R/E | 0.5465 | ambiguous | 0.5917 | pathogenic | -0.044 | Destabilizing | 0.617 | D | 0.383 | neutral | None | None | None | None | N |
| R/F | 0.7728 | likely_pathogenic | 0.8113 | pathogenic | 0.037 | Stabilizing | 0.972 | D | 0.395 | neutral | None | None | None | None | N |
| R/G | 0.2743 | likely_benign | 0.2943 | benign | -0.103 | Destabilizing | 0.004 | N | 0.165 | neutral | N | 0.477594976 | None | None | N |
| R/H | 0.1924 | likely_benign | 0.1797 | benign | -0.723 | Destabilizing | 0.972 | D | 0.389 | neutral | None | None | None | None | N |
| R/I | 0.5732 | likely_pathogenic | 0.6524 | pathogenic | 0.706 | Stabilizing | 0.85 | D | 0.417 | neutral | None | None | None | None | N |
| R/K | 0.151 | likely_benign | 0.1504 | benign | 0.049 | Stabilizing | 0.021 | N | 0.145 | neutral | None | None | None | None | N |
| R/L | 0.454 | ambiguous | 0.5109 | ambiguous | 0.706 | Stabilizing | 0.756 | D | 0.443 | neutral | N | 0.470172031 | None | None | N |
| R/M | 0.4834 | ambiguous | 0.5546 | ambiguous | 0.175 | Stabilizing | 0.992 | D | 0.42 | neutral | None | None | None | None | N |
| R/N | 0.579 | likely_pathogenic | 0.6557 | pathogenic | 0.305 | Stabilizing | 0.617 | D | 0.396 | neutral | None | None | None | None | N |
| R/P | 0.9398 | likely_pathogenic | 0.948 | pathogenic | 0.534 | Stabilizing | 0.985 | D | 0.422 | neutral | D | 0.565897709 | None | None | N |
| R/Q | 0.1606 | likely_benign | 0.1614 | benign | 0.245 | Stabilizing | 0.96 | D | 0.418 | neutral | N | 0.48175846 | None | None | N |
| R/S | 0.5658 | likely_pathogenic | 0.6235 | pathogenic | 0.036 | Stabilizing | 0.447 | N | 0.397 | neutral | None | None | None | None | N |
| R/T | 0.3249 | likely_benign | 0.3685 | ambiguous | 0.259 | Stabilizing | 0.021 | N | 0.242 | neutral | None | None | None | None | N |
| R/V | 0.6375 | likely_pathogenic | 0.6876 | pathogenic | 0.534 | Stabilizing | 0.617 | D | 0.435 | neutral | None | None | None | None | N |
| R/W | 0.3853 | ambiguous | 0.4084 | ambiguous | -0.014 | Destabilizing | 0.992 | D | 0.455 | neutral | None | None | None | None | N |
| R/Y | 0.5691 | likely_pathogenic | 0.6063 | pathogenic | 0.38 | Stabilizing | 0.972 | D | 0.399 | neutral | 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.