Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35029 | 105310;105311;105312 | chr2:178531530;178531529;178531528 | chr2:179396257;179396256;179396255 |
| N2AB | 33388 | 100387;100388;100389 | chr2:178531530;178531529;178531528 | chr2:179396257;179396256;179396255 |
| N2A | 32461 | 97606;97607;97608 | chr2:178531530;178531529;178531528 | chr2:179396257;179396256;179396255 |
| N2B | 25964 | 78115;78116;78117 | chr2:178531530;178531529;178531528 | chr2:179396257;179396256;179396255 |
| Novex-1 | 26089 | 78490;78491;78492 | chr2:178531530;178531529;178531528 | chr2:179396257;179396256;179396255 |
| Novex-2 | 26156 | 78691;78692;78693 | chr2:178531530;178531529;178531528 | chr2:179396257;179396256;179396255 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/W | rs763437247  |
-2.008 | 1.0 | D | 0.893 | 0.673 | 0.834453260621 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| L/W | rs763437247 |
-2.008 | 1.0 | D | 0.893 | 0.673 | 0.834453260621 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/W | rs763437247 |
-2.008 | 1.0 | D | 0.893 | 0.673 | 0.834453260621 | gnomAD-4.0.0 | 5.07475E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.02447E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9745 | likely_pathogenic | 0.9814 | pathogenic | -2.915 | Highly Destabilizing | 0.999 | D | 0.785 | deleterious | None | None | None | None | N |
| L/C | 0.98 | likely_pathogenic | 0.9843 | pathogenic | -2.483 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.545 | Highly Destabilizing | 1.0 | D | 0.9 | deleterious | None | None | None | None | N |
| L/E | 0.9985 | likely_pathogenic | 0.9985 | pathogenic | -3.272 | Highly Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| L/F | 0.9361 | likely_pathogenic | 0.9585 | pathogenic | -1.769 | Destabilizing | 1.0 | D | 0.834 | deleterious | D | 0.524909352 | None | None | N |
| L/G | 0.9971 | likely_pathogenic | 0.9978 | pathogenic | -3.498 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| L/H | 0.9984 | likely_pathogenic | 0.9985 | pathogenic | -3.005 | Highly Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| L/I | 0.4081 | ambiguous | 0.4894 | ambiguous | -1.185 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | N |
| L/K | 0.9975 | likely_pathogenic | 0.9975 | pathogenic | -2.218 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| L/M | 0.5693 | likely_pathogenic | 0.639 | pathogenic | -1.388 | Destabilizing | 1.0 | D | 0.808 | deleterious | D | 0.525416331 | None | None | N |
| L/N | 0.9989 | likely_pathogenic | 0.9991 | pathogenic | -2.773 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| L/P | 0.999 | likely_pathogenic | 0.9993 | pathogenic | -1.749 | Destabilizing | 1.0 | D | 0.897 | deleterious | None | None | None | None | N |
| L/Q | 0.9964 | likely_pathogenic | 0.9967 | pathogenic | -2.549 | Highly Destabilizing | 1.0 | D | 0.912 | deleterious | None | None | None | None | N |
| L/R | 0.9945 | likely_pathogenic | 0.9946 | pathogenic | -2.018 | Highly Destabilizing | 1.0 | D | 0.915 | deleterious | None | None | None | None | N |
| L/S | 0.9982 | likely_pathogenic | 0.9986 | pathogenic | -3.443 | Highly Destabilizing | 1.0 | D | 0.913 | deleterious | D | 0.537533105 | None | None | N |
| L/T | 0.9849 | likely_pathogenic | 0.9884 | pathogenic | -3.014 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| L/V | 0.4626 | ambiguous | 0.5499 | ambiguous | -1.749 | Destabilizing | 0.999 | D | 0.585 | neutral | N | 0.471941897 | None | None | N |
| L/W | 0.996 | likely_pathogenic | 0.9967 | pathogenic | -2.193 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.537533105 | None | None | N |
| L/Y | 0.9967 | likely_pathogenic | 0.9974 | pathogenic | -1.975 | Destabilizing | 1.0 | D | 0.895 | 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.