Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19187 | 57784;57785;57786 | chr2:178595795;178595794;178595793 | chr2:179460522;179460521;179460520 |
| N2AB | 17546 | 52861;52862;52863 | chr2:178595795;178595794;178595793 | chr2:179460522;179460521;179460520 |
| N2A | 16619 | 50080;50081;50082 | chr2:178595795;178595794;178595793 | chr2:179460522;179460521;179460520 |
| N2B | 10122 | 30589;30590;30591 | chr2:178595795;178595794;178595793 | chr2:179460522;179460521;179460520 |
| Novex-1 | 10247 | 30964;30965;30966 | chr2:178595795;178595794;178595793 | chr2:179460522;179460521;179460520 |
| Novex-2 | 10314 | 31165;31166;31167 | chr2:178595795;178595794;178595793 | chr2:179460522;179460521;179460520 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1290770653  |
-2.388 | 0.998 | N | 0.581 | 0.333 | None | gnomAD-2.1.1 | 4.35E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.84E-05 | 0 | 0 |
| V/A | rs1290770653 |
-2.388 | 0.998 | N | 0.581 | 0.333 | None | gnomAD-4.0.0 | 4.8247E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.77758E-05 | 0 | 2.71061E-06 | 2.38663E-05 | 0 |
| V/I | rs764203267 |
-0.487 | 0.949 | N | 0.269 | 0.226 | 0.389126455913 | gnomAD-2.1.1 | 3.08E-05 | None | None | None | None | N | None | 8.79E-05 | 9.05E-05 | None | 0 | 0 | None | 3.63E-05 | None | 0 | 8.5E-06 | 1.49254E-04 |
| V/I | rs764203267 |
-0.487 | 0.949 | N | 0.269 | 0.226 | 0.389126455913 | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | N | None | 1.20855E-04 | 3.93391E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs764203267 |
-0.487 | 0.949 | N | 0.269 | 0.226 | 0.389126455913 | gnomAD-4.0.0 | 1.99748E-05 | None | None | None | None | N | None | 8.03493E-05 | 1.71315E-04 | None | 0 | 0 | None | 1.57505E-05 | 0 | 7.66421E-06 | 3.38906E-05 | 4.83247E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.3078 | likely_benign | 0.3974 | ambiguous | -2.087 | Highly Destabilizing | 0.998 | D | 0.581 | neutral | N | 0.446117271 | None | None | N |
| V/C | 0.8647 | likely_pathogenic | 0.8813 | pathogenic | -1.745 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| V/D | 0.9882 | likely_pathogenic | 0.9916 | pathogenic | -2.825 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | N | 0.462068159 | None | None | N |
| V/E | 0.9723 | likely_pathogenic | 0.9784 | pathogenic | -2.627 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| V/F | 0.8652 | likely_pathogenic | 0.9027 | pathogenic | -1.216 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.499162322 | None | None | N |
| V/G | 0.793 | likely_pathogenic | 0.8268 | pathogenic | -2.614 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | N | 0.499509039 | None | None | N |
| V/H | 0.9931 | likely_pathogenic | 0.9952 | pathogenic | -2.431 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| V/I | 0.1201 | likely_benign | 0.1329 | benign | -0.627 | Destabilizing | 0.949 | D | 0.269 | neutral | N | 0.498468889 | None | None | N |
| V/K | 0.9854 | likely_pathogenic | 0.9886 | pathogenic | -1.876 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| V/L | 0.5939 | likely_pathogenic | 0.6613 | pathogenic | -0.627 | Destabilizing | 0.992 | D | 0.503 | neutral | N | 0.498122172 | None | None | N |
| V/M | 0.6153 | likely_pathogenic | 0.6827 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| V/N | 0.9652 | likely_pathogenic | 0.9748 | pathogenic | -2.129 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| V/P | 0.4645 | ambiguous | 0.5311 | ambiguous | -1.086 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| V/Q | 0.9726 | likely_pathogenic | 0.9782 | pathogenic | -2.004 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| V/R | 0.9754 | likely_pathogenic | 0.9801 | pathogenic | -1.674 | Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| V/S | 0.7559 | likely_pathogenic | 0.8148 | pathogenic | -2.708 | Highly Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| V/T | 0.4597 | ambiguous | 0.5136 | ambiguous | -2.371 | Highly Destabilizing | 0.998 | D | 0.624 | neutral | None | None | None | None | N |
| V/W | 0.9974 | likely_pathogenic | 0.9982 | pathogenic | -1.755 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| V/Y | 0.9903 | likely_pathogenic | 0.994 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.827 | 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.