Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23215 | 69868;69869;69870 | chr2:178576601;178576600;178576599 | chr2:179441328;179441327;179441326 |
| N2AB | 21574 | 64945;64946;64947 | chr2:178576601;178576600;178576599 | chr2:179441328;179441327;179441326 |
| N2A | 20647 | 62164;62165;62166 | chr2:178576601;178576600;178576599 | chr2:179441328;179441327;179441326 |
| N2B | 14150 | 42673;42674;42675 | chr2:178576601;178576600;178576599 | chr2:179441328;179441327;179441326 |
| Novex-1 | 14275 | 43048;43049;43050 | chr2:178576601;178576600;178576599 | chr2:179441328;179441327;179441326 |
| Novex-2 | 14342 | 43249;43250;43251 | chr2:178576601;178576600;178576599 | chr2:179441328;179441327;179441326 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs752195064  |
-1.361 | 0.98 | N | 0.753 | 0.272 | 0.252162846088 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 9.28E-05 | 8.91E-06 | 0 |
| S/N | rs752195064 |
-1.361 | 0.98 | N | 0.753 | 0.272 | 0.252162846088 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| S/N | rs752195064 |
-1.361 | 0.98 | N | 0.753 | 0.272 | 0.252162846088 | gnomAD-4.0.0 | 1.28139E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.56873E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0854 | likely_benign | 0.0919 | benign | -1.314 | Destabilizing | 0.931 | D | 0.56 | neutral | None | None | None | None | N |
| S/C | 0.0687 | likely_benign | 0.0703 | benign | -1.122 | Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.503781495 | None | None | N |
| S/D | 0.8658 | likely_pathogenic | 0.9081 | pathogenic | -2.1 | Highly Destabilizing | 0.985 | D | 0.746 | deleterious | None | None | None | None | N |
| S/E | 0.8344 | likely_pathogenic | 0.8858 | pathogenic | -1.889 | Destabilizing | 0.985 | D | 0.745 | deleterious | None | None | None | None | N |
| S/F | 0.1746 | likely_benign | 0.2009 | benign | -0.827 | Destabilizing | 0.999 | D | 0.818 | deleterious | None | None | None | None | N |
| S/G | 0.1624 | likely_benign | 0.1957 | benign | -1.639 | Destabilizing | 0.98 | D | 0.736 | prob.delet. | N | 0.494904316 | None | None | N |
| S/H | 0.503 | ambiguous | 0.5544 | ambiguous | -1.788 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| S/I | 0.2653 | likely_benign | 0.3327 | benign | -0.475 | Destabilizing | 0.989 | D | 0.784 | deleterious | N | 0.448330857 | None | None | N |
| S/K | 0.8649 | likely_pathogenic | 0.9183 | pathogenic | -0.772 | Destabilizing | 0.97 | D | 0.742 | deleterious | None | None | None | None | N |
| S/L | 0.0864 | likely_benign | 0.1133 | benign | -0.475 | Destabilizing | 0.97 | D | 0.775 | deleterious | None | None | None | None | N |
| S/M | 0.1544 | likely_benign | 0.1692 | benign | -0.828 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| S/N | 0.3799 | ambiguous | 0.4613 | ambiguous | -1.407 | Destabilizing | 0.98 | D | 0.753 | deleterious | N | 0.494397337 | None | None | N |
| S/P | 0.988 | likely_pathogenic | 0.9923 | pathogenic | -0.729 | Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| S/Q | 0.6507 | likely_pathogenic | 0.7047 | pathogenic | -1.022 | Destabilizing | 0.999 | D | 0.778 | deleterious | None | None | None | None | N |
| S/R | 0.7645 | likely_pathogenic | 0.8461 | pathogenic | -1.19 | Destabilizing | 0.994 | D | 0.799 | deleterious | N | 0.432129254 | None | None | N |
| S/T | 0.1072 | likely_benign | 0.1346 | benign | -1.064 | Destabilizing | 0.122 | N | 0.332 | neutral | N | 0.420970898 | None | None | N |
| S/V | 0.2354 | likely_benign | 0.2917 | benign | -0.729 | Destabilizing | 0.97 | D | 0.784 | deleterious | None | None | None | None | N |
| S/W | 0.3019 | likely_benign | 0.373 | ambiguous | -1.25 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| S/Y | 0.181 | likely_benign | 0.2307 | benign | -0.867 | Destabilizing | 0.999 | D | 0.829 | 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.