Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23142 | 69649;69650;69651 | chr2:178576820;178576819;178576818 | chr2:179441547;179441546;179441545 |
| N2AB | 21501 | 64726;64727;64728 | chr2:178576820;178576819;178576818 | chr2:179441547;179441546;179441545 |
| N2A | 20574 | 61945;61946;61947 | chr2:178576820;178576819;178576818 | chr2:179441547;179441546;179441545 |
| N2B | 14077 | 42454;42455;42456 | chr2:178576820;178576819;178576818 | chr2:179441547;179441546;179441545 |
| Novex-1 | 14202 | 42829;42830;42831 | chr2:178576820;178576819;178576818 | chr2:179441547;179441546;179441545 |
| Novex-2 | 14269 | 43030;43031;43032 | chr2:178576820;178576819;178576818 | chr2:179441547;179441546;179441545 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs2288572  |
-0.701 | 0.976 | D | 0.842 | 0.434 | 0.771457117378 | gnomAD-2.1.1 | 4.12E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.7E-05 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs2288572 |
-0.701 | 0.976 | D | 0.842 | 0.434 | 0.771457117378 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93949E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/L | rs2288572 |
-0.701 | 0.976 | D | 0.842 | 0.434 | 0.771457117378 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| P/L | rs2288572 |
-0.701 | 0.976 | D | 0.842 | 0.434 | 0.771457117378 | gnomAD-4.0.0 | 6.5716E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.94401E-04 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | None | None | 0.976 | D | 0.823 | 0.351 | 0.257292322809 | gnomAD-4.0.0 | 1.60543E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86918E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0728 | likely_benign | 0.0733 | benign | -1.509 | Destabilizing | 0.067 | N | 0.513 | neutral | N | 0.473935804 | None | None | N |
| P/C | 0.3816 | ambiguous | 0.3838 | ambiguous | -1.105 | Destabilizing | 0.999 | D | 0.904 | deleterious | None | None | None | None | N |
| P/D | 0.7843 | likely_pathogenic | 0.8104 | pathogenic | -1.682 | Destabilizing | 0.995 | D | 0.849 | deleterious | None | None | None | None | N |
| P/E | 0.4178 | ambiguous | 0.4378 | ambiguous | -1.706 | Destabilizing | 0.991 | D | 0.835 | deleterious | None | None | None | None | N |
| P/F | 0.5151 | ambiguous | 0.524 | ambiguous | -1.297 | Destabilizing | 0.999 | D | 0.906 | deleterious | None | None | None | None | N |
| P/G | 0.4206 | ambiguous | 0.4378 | ambiguous | -1.795 | Destabilizing | 0.938 | D | 0.822 | deleterious | None | None | None | None | N |
| P/H | 0.2578 | likely_benign | 0.2738 | benign | -1.332 | Destabilizing | 0.999 | D | 0.891 | deleterious | D | 0.535751316 | None | None | N |
| P/I | 0.3507 | ambiguous | 0.3688 | ambiguous | -0.826 | Destabilizing | 0.991 | D | 0.876 | deleterious | None | None | None | None | N |
| P/K | 0.2905 | likely_benign | 0.3238 | benign | -1.189 | Destabilizing | 0.991 | D | 0.843 | deleterious | None | None | None | None | N |
| P/L | 0.1759 | likely_benign | 0.1964 | benign | -0.826 | Destabilizing | 0.976 | D | 0.842 | deleterious | D | 0.524141521 | None | None | N |
| P/M | 0.3242 | likely_benign | 0.3312 | benign | -0.639 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| P/N | 0.5657 | likely_pathogenic | 0.5741 | pathogenic | -0.987 | Destabilizing | 0.995 | D | 0.865 | deleterious | None | None | None | None | N |
| P/Q | 0.1683 | likely_benign | 0.1777 | benign | -1.237 | Destabilizing | 0.995 | D | 0.86 | deleterious | None | None | None | None | N |
| P/R | 0.171 | likely_benign | 0.2012 | benign | -0.641 | Destabilizing | 0.994 | D | 0.87 | deleterious | N | 0.511353184 | None | None | N |
| P/S | 0.1562 | likely_benign | 0.1599 | benign | -1.455 | Destabilizing | 0.976 | D | 0.823 | deleterious | D | 0.524119482 | None | None | N |
| P/T | 0.1831 | likely_benign | 0.1942 | benign | -1.38 | Destabilizing | 0.988 | D | 0.835 | deleterious | N | 0.508492802 | None | None | N |
| P/V | 0.2464 | likely_benign | 0.2592 | benign | -1.02 | Destabilizing | 0.982 | D | 0.834 | deleterious | None | None | None | None | N |
| P/W | 0.7142 | likely_pathogenic | 0.7295 | pathogenic | -1.448 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| P/Y | 0.5525 | ambiguous | 0.5645 | pathogenic | -1.164 | Destabilizing | 1.0 | D | 0.908 | 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.