Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31574 | 94945;94946;94947 | chr2:178546708;178546707;178546706 | chr2:179411435;179411434;179411433 |
| N2AB | 29933 | 90022;90023;90024 | chr2:178546708;178546707;178546706 | chr2:179411435;179411434;179411433 |
| N2A | 29006 | 87241;87242;87243 | chr2:178546708;178546707;178546706 | chr2:179411435;179411434;179411433 |
| N2B | 22509 | 67750;67751;67752 | chr2:178546708;178546707;178546706 | chr2:179411435;179411434;179411433 |
| Novex-1 | 22634 | 68125;68126;68127 | chr2:178546708;178546707;178546706 | chr2:179411435;179411434;179411433 |
| Novex-2 | 22701 | 68326;68327;68328 | chr2:178546708;178546707;178546706 | chr2:179411435;179411434;179411433 |
| 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/F | rs759654688  |
-2.357 | 1.0 | D | 0.887 | 0.658 | 0.858370218828 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| L/F | rs759654688 |
-2.357 | 1.0 | D | 0.887 | 0.658 | 0.858370218828 | gnomAD-4.0.0 | 3.18255E-06 | None | None | None | None | N | None | 0 | 4.57331E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/V | rs759654688 |
-2.018 | 0.999 | D | 0.851 | 0.618 | 0.821234274979 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/V | rs759654688 |
-2.018 | 0.999 | D | 0.851 | 0.618 | 0.821234274979 | gnomAD-4.0.0 | 4.77383E-06 | None | None | None | None | N | None | 0 | 6.85997E-05 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9692 | likely_pathogenic | 0.9515 | pathogenic | -2.379 | Highly Destabilizing | 0.999 | D | 0.855 | deleterious | None | None | None | None | N |
| L/C | 0.9473 | likely_pathogenic | 0.9252 | pathogenic | -2.151 | Highly Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -1.903 | Destabilizing | 1.0 | D | 0.904 | deleterious | None | None | None | None | N |
| L/E | 0.9987 | likely_pathogenic | 0.9981 | pathogenic | -1.823 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| L/F | 0.9586 | likely_pathogenic | 0.9334 | pathogenic | -1.816 | Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.657082644 | None | None | N |
| L/G | 0.9958 | likely_pathogenic | 0.9933 | pathogenic | -2.789 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| L/H | 0.9981 | likely_pathogenic | 0.9968 | pathogenic | -1.927 | Destabilizing | 1.0 | D | 0.853 | deleterious | D | 0.683427972 | None | None | N |
| L/I | 0.546 | ambiguous | 0.5134 | ambiguous | -1.266 | Destabilizing | 0.999 | D | 0.831 | deleterious | D | 0.617069961 | None | None | N |
| L/K | 0.9978 | likely_pathogenic | 0.9968 | pathogenic | -1.696 | Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | None | N |
| L/M | 0.7195 | likely_pathogenic | 0.665 | pathogenic | -1.223 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | N |
| L/N | 0.9979 | likely_pathogenic | 0.9968 | pathogenic | -1.716 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| L/P | 0.9975 | likely_pathogenic | 0.9959 | pathogenic | -1.61 | Destabilizing | 1.0 | D | 0.905 | deleterious | D | 0.667176447 | None | None | N |
| L/Q | 0.9951 | likely_pathogenic | 0.9919 | pathogenic | -1.834 | Destabilizing | 1.0 | D | 0.905 | deleterious | None | None | None | None | N |
| L/R | 0.9939 | likely_pathogenic | 0.9912 | pathogenic | -1.123 | Destabilizing | 1.0 | D | 0.898 | deleterious | D | 0.667176447 | None | None | N |
| L/S | 0.9978 | likely_pathogenic | 0.996 | pathogenic | -2.511 | Highly Destabilizing | 1.0 | D | 0.884 | deleterious | None | None | None | None | N |
| L/T | 0.9867 | likely_pathogenic | 0.9788 | pathogenic | -2.288 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| L/V | 0.5715 | likely_pathogenic | 0.5039 | ambiguous | -1.61 | Destabilizing | 0.999 | D | 0.851 | deleterious | D | 0.5960537 | None | None | N |
| L/W | 0.9982 | likely_pathogenic | 0.9971 | pathogenic | -1.866 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| L/Y | 0.9974 | likely_pathogenic | 0.9958 | pathogenic | -1.651 | Destabilizing | 1.0 | D | 0.874 | 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.