Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35653 | 107182;107183;107184 | chr2:178528794;178528793;178528792 | chr2:179393521;179393520;179393519 |
| N2AB | 34012 | 102259;102260;102261 | chr2:178528794;178528793;178528792 | chr2:179393521;179393520;179393519 |
| N2A | 33085 | 99478;99479;99480 | chr2:178528794;178528793;178528792 | chr2:179393521;179393520;179393519 |
| N2B | 26588 | 79987;79988;79989 | chr2:178528794;178528793;178528792 | chr2:179393521;179393520;179393519 |
| Novex-1 | 26713 | 80362;80363;80364 | chr2:178528794;178528793;178528792 | chr2:179393521;179393520;179393519 |
| Novex-2 | 26780 | 80563;80564;80565 | chr2:178528794;178528793;178528792 | chr2:179393521;179393520;179393519 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/D | rs886042500  |
-2.283 | 0.996 | N | 0.801 | 0.599 | 0.631970868704 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| Y/D | rs886042500 |
-2.283 | 0.996 | N | 0.801 | 0.599 | 0.631970868704 | 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 |
| Y/D | rs886042500 |
-2.283 | 0.996 | N | 0.801 | 0.599 | 0.631970868704 | gnomAD-4.0.0 | 2.05115E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.83268E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.8239 | likely_pathogenic | 0.8633 | pathogenic | -2.346 | Highly Destabilizing | 0.944 | D | 0.651 | neutral | None | None | None | None | N |
| Y/C | 0.3891 | ambiguous | 0.4332 | ambiguous | -1.344 | Destabilizing | 0.999 | D | 0.787 | deleterious | N | 0.483534801 | None | None | N |
| Y/D | 0.6983 | likely_pathogenic | 0.7996 | pathogenic | -0.811 | Destabilizing | 0.996 | D | 0.801 | deleterious | N | 0.483708159 | None | None | N |
| Y/E | 0.9034 | likely_pathogenic | 0.9354 | pathogenic | -0.677 | Destabilizing | 0.997 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/F | 0.1716 | likely_benign | 0.16 | benign | -0.947 | Destabilizing | 0.039 | N | 0.329 | neutral | N | 0.482321293 | None | None | N |
| Y/G | 0.7262 | likely_pathogenic | 0.8039 | pathogenic | -2.706 | Highly Destabilizing | 0.992 | D | 0.779 | deleterious | None | None | None | None | N |
| Y/H | 0.4968 | ambiguous | 0.5533 | ambiguous | -1.167 | Destabilizing | 0.996 | D | 0.714 | prob.delet. | N | 0.483534801 | None | None | N |
| Y/I | 0.7709 | likely_pathogenic | 0.8009 | pathogenic | -1.232 | Destabilizing | 0.968 | D | 0.703 | prob.neutral | None | None | None | None | N |
| Y/K | 0.8669 | likely_pathogenic | 0.9119 | pathogenic | -1.178 | Destabilizing | 0.992 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/L | 0.6626 | likely_pathogenic | 0.7125 | pathogenic | -1.232 | Destabilizing | 0.895 | D | 0.523 | neutral | None | None | None | None | N |
| Y/M | 0.8454 | likely_pathogenic | 0.8687 | pathogenic | -1.065 | Destabilizing | 0.998 | D | 0.749 | deleterious | None | None | None | None | N |
| Y/N | 0.4602 | ambiguous | 0.5503 | ambiguous | -1.534 | Destabilizing | 0.996 | D | 0.781 | deleterious | N | 0.483534801 | None | None | N |
| Y/P | 0.8937 | likely_pathogenic | 0.94 | pathogenic | -1.602 | Destabilizing | 0.997 | D | 0.809 | deleterious | None | None | None | None | N |
| Y/Q | 0.8519 | likely_pathogenic | 0.8977 | pathogenic | -1.392 | Destabilizing | 0.997 | D | 0.769 | deleterious | None | None | None | None | N |
| Y/R | 0.7607 | likely_pathogenic | 0.8341 | pathogenic | -0.872 | Destabilizing | 0.992 | D | 0.783 | deleterious | None | None | None | None | N |
| Y/S | 0.5214 | ambiguous | 0.6155 | pathogenic | -2.227 | Highly Destabilizing | 0.989 | D | 0.751 | deleterious | N | 0.483014726 | None | None | N |
| Y/T | 0.7684 | likely_pathogenic | 0.8202 | pathogenic | -1.985 | Destabilizing | 0.992 | D | 0.757 | deleterious | None | None | None | None | N |
| Y/V | 0.6911 | likely_pathogenic | 0.7326 | pathogenic | -1.602 | Destabilizing | 0.895 | D | 0.652 | neutral | None | None | None | None | N |
| Y/W | 0.6047 | likely_pathogenic | 0.6201 | pathogenic | -0.414 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | 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.