Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22926 | 69001;69002;69003 | chr2:178577650;178577649;178577648 | chr2:179442377;179442376;179442375 |
| N2AB | 21285 | 64078;64079;64080 | chr2:178577650;178577649;178577648 | chr2:179442377;179442376;179442375 |
| N2A | 20358 | 61297;61298;61299 | chr2:178577650;178577649;178577648 | chr2:179442377;179442376;179442375 |
| N2B | 13861 | 41806;41807;41808 | chr2:178577650;178577649;178577648 | chr2:179442377;179442376;179442375 |
| Novex-1 | 13986 | 42181;42182;42183 | chr2:178577650;178577649;178577648 | chr2:179442377;179442376;179442375 |
| Novex-2 | 14053 | 42382;42383;42384 | chr2:178577650;178577649;178577648 | chr2:179442377;179442376;179442375 |
| 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 | rs958609992  |
None | 0.822 | D | 0.759 | 0.324 | 0.256793551483 | gnomAD-4.0.0 | 1.36913E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99696E-07 | 1.16117E-05 | 0 |
| S/R | rs753624630 |
-0.821 | 0.942 | D | 0.815 | 0.422 | 0.352262096564 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs753624630 |
-0.821 | 0.942 | D | 0.815 | 0.422 | 0.352262096564 | gnomAD-4.0.0 | 3.18609E-06 | None | None | None | None | N | None | 0 | 4.57792E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.6232 | likely_pathogenic | 0.6038 | pathogenic | -0.673 | Destabilizing | 0.559 | D | 0.671 | neutral | None | None | None | None | N |
| S/C | 0.8398 | likely_pathogenic | 0.8328 | pathogenic | -0.659 | Destabilizing | 0.997 | D | 0.774 | deleterious | D | 0.556199429 | None | None | N |
| S/D | 0.9952 | likely_pathogenic | 0.9938 | pathogenic | -0.936 | Destabilizing | 0.86 | D | 0.765 | deleterious | None | None | None | None | N |
| S/E | 0.9979 | likely_pathogenic | 0.9975 | pathogenic | -0.867 | Destabilizing | 0.86 | D | 0.766 | deleterious | None | None | None | None | N |
| S/F | 0.9968 | likely_pathogenic | 0.9961 | pathogenic | -0.509 | Destabilizing | 0.978 | D | 0.849 | deleterious | None | None | None | None | N |
| S/G | 0.4062 | ambiguous | 0.294 | benign | -0.991 | Destabilizing | 0.014 | N | 0.441 | neutral | N | 0.516027569 | None | None | N |
| S/H | 0.9944 | likely_pathogenic | 0.9928 | pathogenic | -1.428 | Destabilizing | 0.998 | D | 0.779 | deleterious | None | None | None | None | N |
| S/I | 0.9936 | likely_pathogenic | 0.9921 | pathogenic | 0.089 | Stabilizing | 0.942 | D | 0.862 | deleterious | D | 0.55569245 | None | None | N |
| S/K | 0.9995 | likely_pathogenic | 0.9993 | pathogenic | -0.911 | Destabilizing | 0.86 | D | 0.765 | deleterious | None | None | None | None | N |
| S/L | 0.9682 | likely_pathogenic | 0.9634 | pathogenic | 0.089 | Stabilizing | 0.754 | D | 0.837 | deleterious | None | None | None | None | N |
| S/M | 0.9877 | likely_pathogenic | 0.9839 | pathogenic | 0.123 | Stabilizing | 0.998 | D | 0.779 | deleterious | None | None | None | None | N |
| S/N | 0.9841 | likely_pathogenic | 0.9806 | pathogenic | -1.084 | Destabilizing | 0.822 | D | 0.759 | deleterious | D | 0.55543896 | None | None | N |
| S/P | 0.9925 | likely_pathogenic | 0.9922 | pathogenic | -0.13 | Destabilizing | 0.978 | D | 0.811 | deleterious | None | None | None | None | N |
| S/Q | 0.9969 | likely_pathogenic | 0.996 | pathogenic | -1.09 | Destabilizing | 0.978 | D | 0.747 | deleterious | None | None | None | None | N |
| S/R | 0.9989 | likely_pathogenic | 0.9985 | pathogenic | -0.916 | Destabilizing | 0.942 | D | 0.815 | deleterious | D | 0.543068697 | None | None | N |
| S/T | 0.7922 | likely_pathogenic | 0.7651 | pathogenic | -0.933 | Destabilizing | 0.014 | N | 0.471 | neutral | D | 0.555185471 | None | None | N |
| S/V | 0.9899 | likely_pathogenic | 0.9886 | pathogenic | -0.13 | Destabilizing | 0.915 | D | 0.837 | deleterious | None | None | None | None | N |
| S/W | 0.9964 | likely_pathogenic | 0.9961 | pathogenic | -0.617 | Destabilizing | 0.998 | D | 0.885 | deleterious | None | None | None | None | N |
| S/Y | 0.9936 | likely_pathogenic | 0.9929 | pathogenic | -0.31 | Destabilizing | 0.993 | D | 0.863 | 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.