Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16333 | 49222;49223;49224 | chr2:178614517;178614516;178614515 | chr2:179479244;179479243;179479242 |
| N2AB | 14692 | 44299;44300;44301 | chr2:178614517;178614516;178614515 | chr2:179479244;179479243;179479242 |
| N2A | 13765 | 41518;41519;41520 | chr2:178614517;178614516;178614515 | chr2:179479244;179479243;179479242 |
| N2B | 7268 | 22027;22028;22029 | chr2:178614517;178614516;178614515 | chr2:179479244;179479243;179479242 |
| Novex-1 | 7393 | 22402;22403;22404 | chr2:178614517;178614516;178614515 | chr2:179479244;179479243;179479242 |
| Novex-2 | 7460 | 22603;22604;22605 | chr2:178614517;178614516;178614515 | chr2:179479244;179479243;179479242 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs756253347  |
-1.62 | 1.0 | D | 0.555 | 0.691 | 0.737821564749 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 0 | 0 |
| A/S | rs756253347 |
-1.62 | 1.0 | D | 0.555 | 0.691 | 0.737821564749 | gnomAD-4.0.0 | 1.59482E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.79018E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | None | None | 1.0 | D | 0.62 | 0.626 | 0.740653843246 | gnomAD-4.0.0 | 1.3697E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79994E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.9049 | likely_pathogenic | 0.8973 | pathogenic | -1.169 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | I |
| A/D | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -2.024 | Highly Destabilizing | 1.0 | D | 0.847 | deleterious | D | 0.829211067 | None | None | I |
| A/E | 0.9983 | likely_pathogenic | 0.9981 | pathogenic | -2.0 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| A/F | 0.9962 | likely_pathogenic | 0.9964 | pathogenic | -1.063 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| A/G | 0.4941 | ambiguous | 0.4723 | ambiguous | -1.428 | Destabilizing | 1.0 | D | 0.54 | neutral | D | 0.716495527 | None | None | I |
| A/H | 0.9995 | likely_pathogenic | 0.9994 | pathogenic | -1.724 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| A/I | 0.9345 | likely_pathogenic | 0.9514 | pathogenic | -0.376 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| A/K | 0.9996 | likely_pathogenic | 0.9994 | pathogenic | -1.479 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | I |
| A/L | 0.858 | likely_pathogenic | 0.8827 | pathogenic | -0.376 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| A/M | 0.9501 | likely_pathogenic | 0.958 | pathogenic | -0.37 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| A/N | 0.9976 | likely_pathogenic | 0.9973 | pathogenic | -1.338 | Destabilizing | 1.0 | D | 0.838 | deleterious | None | None | None | None | I |
| A/P | 0.9991 | likely_pathogenic | 0.9991 | pathogenic | -0.581 | Destabilizing | 1.0 | D | 0.842 | deleterious | D | 0.759569849 | None | None | I |
| A/Q | 0.9977 | likely_pathogenic | 0.9972 | pathogenic | -1.441 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| A/R | 0.9984 | likely_pathogenic | 0.998 | pathogenic | -1.197 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| A/S | 0.7133 | likely_pathogenic | 0.7054 | pathogenic | -1.653 | Destabilizing | 1.0 | D | 0.555 | neutral | D | 0.775125514 | None | None | I |
| A/T | 0.8428 | likely_pathogenic | 0.8637 | pathogenic | -1.54 | Destabilizing | 1.0 | D | 0.748 | deleterious | D | 0.738965919 | None | None | I |
| A/V | 0.6929 | likely_pathogenic | 0.7585 | pathogenic | -0.581 | Destabilizing | 1.0 | D | 0.62 | neutral | D | 0.591327676 | None | None | I |
| A/W | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.545 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | I |
| A/Y | 0.9987 | likely_pathogenic | 0.9985 | pathogenic | -1.119 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | I |
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.