Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22762 | 68509;68510;68511 | chr2:178578656;178578655;178578654 | chr2:179443383;179443382;179443381 |
| N2AB | 21121 | 63586;63587;63588 | chr2:178578656;178578655;178578654 | chr2:179443383;179443382;179443381 |
| N2A | 20194 | 60805;60806;60807 | chr2:178578656;178578655;178578654 | chr2:179443383;179443382;179443381 |
| N2B | 13697 | 41314;41315;41316 | chr2:178578656;178578655;178578654 | chr2:179443383;179443382;179443381 |
| Novex-1 | 13822 | 41689;41690;41691 | chr2:178578656;178578655;178578654 | chr2:179443383;179443382;179443381 |
| Novex-2 | 13889 | 41890;41891;41892 | chr2:178578656;178578655;178578654 | chr2:179443383;179443382;179443381 |
| 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/P | rs1359881893  |
-1.272 | 1.0 | D | 0.863 | 0.821 | 0.886502306561 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.04069E-04 | None | 0 | None | 0 | 0 | 1.41683E-04 |
| L/P | rs1359881893 |
-1.272 | 1.0 | D | 0.863 | 0.821 | 0.886502306561 | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.16189E-03 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs1359881893 |
-1.272 | 1.0 | D | 0.863 | 0.821 | 0.886502306561 | gnomAD-4.0.0 | 5.27282E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.90515E-03 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | None | None | 1.0 | D | 0.823 | 0.8 | 0.864855109137 | gnomAD-4.0.0 | 6.84962E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.001E-07 | 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 | 0.8742 | likely_pathogenic | 0.8729 | pathogenic | -2.483 | Highly Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| L/C | 0.7863 | likely_pathogenic | 0.7956 | pathogenic | -1.609 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| L/D | 0.9994 | likely_pathogenic | 0.9995 | pathogenic | -3.087 | Highly Destabilizing | 1.0 | D | 0.86 | deleterious | None | None | None | None | N |
| L/E | 0.995 | likely_pathogenic | 0.9961 | pathogenic | -2.757 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| L/F | 0.6648 | likely_pathogenic | 0.705 | pathogenic | -1.434 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| L/G | 0.9865 | likely_pathogenic | 0.9876 | pathogenic | -3.11 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| L/H | 0.988 | likely_pathogenic | 0.9909 | pathogenic | -2.879 | Highly Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| L/I | 0.0924 | likely_benign | 0.0883 | benign | -0.61 | Destabilizing | 0.999 | D | 0.533 | neutral | N | 0.463113882 | None | None | N |
| L/K | 0.9933 | likely_pathogenic | 0.9952 | pathogenic | -1.831 | Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| L/M | 0.254 | likely_benign | 0.2475 | benign | -0.747 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| L/N | 0.995 | likely_pathogenic | 0.996 | pathogenic | -2.522 | Highly Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| L/P | 0.9947 | likely_pathogenic | 0.9954 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.543497814 | None | None | N |
| L/Q | 0.9803 | likely_pathogenic | 0.9837 | pathogenic | -2.146 | Highly Destabilizing | 1.0 | D | 0.844 | deleterious | D | 0.543497814 | None | None | N |
| L/R | 0.9854 | likely_pathogenic | 0.989 | pathogenic | -1.964 | Destabilizing | 1.0 | D | 0.823 | deleterious | D | 0.543497814 | None | None | N |
| L/S | 0.9836 | likely_pathogenic | 0.9846 | pathogenic | -3.106 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| L/T | 0.9125 | likely_pathogenic | 0.9098 | pathogenic | -2.605 | Highly Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| L/V | 0.0855 | likely_benign | 0.0819 | benign | -1.223 | Destabilizing | 0.999 | D | 0.55 | neutral | N | 0.447680283 | None | None | N |
| L/W | 0.979 | likely_pathogenic | 0.9856 | pathogenic | -1.879 | Destabilizing | 1.0 | D | 0.769 | deleterious | None | None | None | None | N |
| L/Y | 0.9754 | likely_pathogenic | 0.9826 | pathogenic | -1.591 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | 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.