Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24001 | 72226;72227;72228 | chr2:178574131;178574130;178574129 | chr2:179438858;179438857;179438856 |
| N2AB | 22360 | 67303;67304;67305 | chr2:178574131;178574130;178574129 | chr2:179438858;179438857;179438856 |
| N2A | 21433 | 64522;64523;64524 | chr2:178574131;178574130;178574129 | chr2:179438858;179438857;179438856 |
| N2B | 14936 | 45031;45032;45033 | chr2:178574131;178574130;178574129 | chr2:179438858;179438857;179438856 |
| Novex-1 | 15061 | 45406;45407;45408 | chr2:178574131;178574130;178574129 | chr2:179438858;179438857;179438856 |
| Novex-2 | 15128 | 45607;45608;45609 | chr2:178574131;178574130;178574129 | chr2:179438858;179438857;179438856 |
| 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 | None | None | 0.999 | D | 0.62 | 0.596 | 0.592542363097 | gnomAD-4.0.0 | 6.84309E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99588E-07 | 0 | 0 |
| A/T | rs180828370  |
-1.828 | 1.0 | D | 0.713 | 0.621 | None | gnomAD-2.1.1 | 1.75285E-04 | None | None | None | None | N | None | 1.03349E-03 | 6.50821E-04 | None | 0 | 0 | None | 0 | None | 0 | 7.84E-06 | 0 |
| A/T | rs180828370 |
-1.828 | 1.0 | D | 0.713 | 0.621 | None | gnomAD-3.1.2 | 2.82783E-04 | None | None | None | None | N | None | 9.89334E-04 | 1.3113E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs180828370 |
-1.828 | 1.0 | D | 0.713 | 0.621 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 8E-04 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/T | rs180828370 |
-1.828 | 1.0 | D | 0.713 | 0.621 | None | gnomAD-4.0.0 | 6.19768E-05 | None | None | None | None | N | None | 9.59718E-04 | 3.83423E-04 | None | 0 | 0 | None | 0 | 0 | 1.69548E-06 | 0 | 4.80261E-05 |
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 | 0.8091 | likely_pathogenic | 0.8207 | pathogenic | -1.424 | Destabilizing | 0.844 | D | 0.462 | neutral | None | None | None | None | N |
| A/D | 0.9978 | likely_pathogenic | 0.9973 | pathogenic | -2.776 | Highly Destabilizing | 1.0 | D | 0.771 | deleterious | D | 0.581323528 | None | None | N |
| A/E | 0.9941 | likely_pathogenic | 0.9924 | pathogenic | -2.51 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| A/F | 0.9853 | likely_pathogenic | 0.9848 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| A/G | 0.5505 | ambiguous | 0.5327 | ambiguous | -2.163 | Highly Destabilizing | 0.998 | D | 0.623 | neutral | D | 0.549835052 | None | None | N |
| A/H | 0.9967 | likely_pathogenic | 0.996 | pathogenic | -2.352 | Highly Destabilizing | 1.0 | D | 0.804 | deleterious | None | None | None | None | N |
| A/I | 0.9443 | likely_pathogenic | 0.9478 | pathogenic | -0.268 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | N |
| A/K | 0.9987 | likely_pathogenic | 0.9984 | pathogenic | -1.353 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| A/L | 0.8793 | likely_pathogenic | 0.8771 | pathogenic | -0.268 | Destabilizing | 0.997 | D | 0.733 | prob.delet. | None | None | None | None | N |
| A/M | 0.9436 | likely_pathogenic | 0.9473 | pathogenic | -0.702 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/N | 0.9923 | likely_pathogenic | 0.9911 | pathogenic | -1.863 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| A/P | 0.9859 | likely_pathogenic | 0.9839 | pathogenic | -0.698 | Destabilizing | 1.0 | D | 0.785 | deleterious | D | 0.554318503 | None | None | N |
| A/Q | 0.9862 | likely_pathogenic | 0.9827 | pathogenic | -1.535 | Destabilizing | 1.0 | D | 0.816 | deleterious | None | None | None | None | N |
| A/R | 0.9933 | likely_pathogenic | 0.9915 | pathogenic | -1.549 | Destabilizing | 1.0 | D | 0.778 | deleterious | None | None | None | None | N |
| A/S | 0.3197 | likely_benign | 0.3247 | benign | -2.237 | Highly Destabilizing | 0.999 | D | 0.62 | neutral | D | 0.529324487 | None | None | N |
| A/T | 0.6086 | likely_pathogenic | 0.6378 | pathogenic | -1.846 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | D | 0.580056081 | None | None | N |
| A/V | 0.7518 | likely_pathogenic | 0.7601 | pathogenic | -0.698 | Destabilizing | 0.996 | D | 0.643 | neutral | D | 0.543758665 | None | None | N |
| A/W | 0.9987 | likely_pathogenic | 0.9986 | pathogenic | -1.557 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| A/Y | 0.9953 | likely_pathogenic | 0.9946 | pathogenic | -1.144 | Destabilizing | 1.0 | D | 0.829 | 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.