Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15070 | 45433;45434;45435 | chr2:178621616;178621615;178621614 | chr2:179486343;179486342;179486341 |
| N2AB | 13429 | 40510;40511;40512 | chr2:178621616;178621615;178621614 | chr2:179486343;179486342;179486341 |
| N2A | 12502 | 37729;37730;37731 | chr2:178621616;178621615;178621614 | chr2:179486343;179486342;179486341 |
| N2B | 6005 | 18238;18239;18240 | chr2:178621616;178621615;178621614 | chr2:179486343;179486342;179486341 |
| Novex-1 | 6130 | 18613;18614;18615 | chr2:178621616;178621615;178621614 | chr2:179486343;179486342;179486341 |
| Novex-2 | 6197 | 18814;18815;18816 | chr2:178621616;178621615;178621614 | chr2:179486343;179486342;179486341 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs749782273  |
-0.837 | 0.772 | D | 0.59 | 0.176 | 0.614179585095 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| I/M | rs749782273 |
-0.837 | 0.772 | D | 0.59 | 0.176 | 0.614179585095 | gnomAD-4.0.0 | 1.59372E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43324E-05 | 0 |
| I/T | None | None | 0.491 | D | 0.577 | 0.512 | 0.747713835963 | gnomAD-4.0.0 | 1.59368E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86269E-06 | 0 | 0 |
| I/V | rs757799030 |
-1.34 | None | N | 0.153 | 0.143 | 0.433713641954 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs757799030 |
-1.34 | None | N | 0.153 | 0.143 | 0.433713641954 | gnomAD-4.0.0 | 9.56215E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.66945E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.904 | likely_pathogenic | 0.8415 | pathogenic | -2.197 | Highly Destabilizing | 0.209 | N | 0.498 | neutral | None | None | None | None | N |
| I/C | 0.9506 | likely_pathogenic | 0.9189 | pathogenic | -1.344 | Destabilizing | 0.965 | D | 0.61 | neutral | None | None | None | None | N |
| I/D | 0.985 | likely_pathogenic | 0.9745 | pathogenic | -3.033 | Highly Destabilizing | 0.965 | D | 0.655 | neutral | None | None | None | None | N |
| I/E | 0.9635 | likely_pathogenic | 0.9443 | pathogenic | -2.759 | Highly Destabilizing | 0.901 | D | 0.675 | prob.neutral | None | None | None | None | N |
| I/F | 0.5027 | ambiguous | 0.3804 | ambiguous | -1.492 | Destabilizing | 0.491 | N | 0.571 | neutral | D | 0.588564077 | None | None | N |
| I/G | 0.9742 | likely_pathogenic | 0.9573 | pathogenic | -2.703 | Highly Destabilizing | 0.722 | D | 0.651 | neutral | None | None | None | None | N |
| I/H | 0.9586 | likely_pathogenic | 0.9251 | pathogenic | -2.373 | Highly Destabilizing | 0.991 | D | 0.642 | neutral | None | None | None | None | N |
| I/K | 0.9162 | likely_pathogenic | 0.8711 | pathogenic | -1.761 | Destabilizing | 0.722 | D | 0.654 | neutral | None | None | None | None | N |
| I/L | 0.1873 | likely_benign | 0.1501 | benign | -0.694 | Destabilizing | None | N | 0.141 | neutral | N | 0.404570413 | None | None | N |
| I/M | 0.2041 | likely_benign | 0.1525 | benign | -0.677 | Destabilizing | 0.772 | D | 0.59 | neutral | D | 0.537739124 | None | None | N |
| I/N | 0.8475 | likely_pathogenic | 0.7758 | pathogenic | -2.384 | Highly Destabilizing | 0.954 | D | 0.676 | prob.neutral | D | 0.620120269 | None | None | N |
| I/P | 0.9864 | likely_pathogenic | 0.9795 | pathogenic | -1.185 | Destabilizing | 0.965 | D | 0.661 | neutral | None | None | None | None | N |
| I/Q | 0.9372 | likely_pathogenic | 0.9048 | pathogenic | -2.119 | Highly Destabilizing | 0.965 | D | 0.684 | prob.neutral | None | None | None | None | N |
| I/R | 0.8915 | likely_pathogenic | 0.8335 | pathogenic | -1.794 | Destabilizing | 0.901 | D | 0.662 | neutral | None | None | None | None | N |
| I/S | 0.9319 | likely_pathogenic | 0.8813 | pathogenic | -2.863 | Highly Destabilizing | 0.491 | N | 0.631 | neutral | D | 0.659573034 | None | None | N |
| I/T | 0.8913 | likely_pathogenic | 0.8109 | pathogenic | -2.442 | Highly Destabilizing | 0.491 | N | 0.577 | neutral | D | 0.654312362 | None | None | N |
| I/V | 0.1699 | likely_benign | 0.1361 | benign | -1.185 | Destabilizing | None | N | 0.153 | neutral | N | 0.488306849 | None | None | N |
| I/W | 0.9639 | likely_pathogenic | 0.9395 | pathogenic | -1.879 | Destabilizing | 0.991 | D | 0.655 | neutral | None | None | None | None | N |
| I/Y | 0.8757 | likely_pathogenic | 0.8191 | pathogenic | -1.556 | Destabilizing | 0.901 | D | 0.64 | 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.