Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23961 | 72106;72107;72108 | chr2:178574251;178574250;178574249 | chr2:179438978;179438977;179438976 |
| N2AB | 22320 | 67183;67184;67185 | chr2:178574251;178574250;178574249 | chr2:179438978;179438977;179438976 |
| N2A | 21393 | 64402;64403;64404 | chr2:178574251;178574250;178574249 | chr2:179438978;179438977;179438976 |
| N2B | 14896 | 44911;44912;44913 | chr2:178574251;178574250;178574249 | chr2:179438978;179438977;179438976 |
| Novex-1 | 15021 | 45286;45287;45288 | chr2:178574251;178574250;178574249 | chr2:179438978;179438977;179438976 |
| Novex-2 | 15088 | 45487;45488;45489 | chr2:178574251;178574250;178574249 | chr2:179438978;179438977;179438976 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs886042407  |
-2.48 | 0.977 | D | 0.652 | 0.587 | 0.705890645922 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| V/A | rs886042407 |
-2.48 | 0.977 | D | 0.652 | 0.587 | 0.705890645922 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/A | rs886042407 |
-2.48 | 0.977 | D | 0.652 | 0.587 | 0.705890645922 | gnomAD-4.0.0 | 2.91428E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.90108E-05 | 0 | 1.602E-05 |
| V/I | rs397517690 |
-0.307 | 0.428 | N | 0.289 | 0.18 | 0.445007932271 | gnomAD-2.1.1 | 1.69564E-04 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 5.62E-05 | None | 1.14476E-03 | None | 0 | 4.47E-05 | 0 |
| V/I | rs397517690 |
-0.307 | 0.428 | N | 0.289 | 0.18 | 0.445007932271 | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.86258E-03 | 0 |
| V/I | rs397517690 |
-0.307 | 0.428 | N | 0.289 | 0.18 | 0.445007932271 | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 3.1E-03 | None |
| V/I | rs397517690 |
-0.307 | 0.428 | N | 0.289 | 0.18 | 0.445007932271 | gnomAD-4.0.0 | 6.94406E-05 | None | None | None | None | N | None | 4E-05 | 1.66711E-05 | None | 0 | 6.71081E-05 | None | 0 | 0 | 1.01766E-05 | 9.88424E-04 | 4.80384E-05 |
| V/L | rs397517690 |
-0.31 | 0.957 | D | 0.621 | 0.337 | 0.567569374525 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.62E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7985 | likely_pathogenic | 0.8476 | pathogenic | -2.456 | Highly Destabilizing | 0.977 | D | 0.652 | neutral | D | 0.537527241 | None | None | N |
| V/C | 0.9789 | likely_pathogenic | 0.9821 | pathogenic | -1.588 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| V/D | 0.9989 | likely_pathogenic | 0.9989 | pathogenic | -3.327 | Highly Destabilizing | 0.999 | D | 0.895 | deleterious | D | 0.561164904 | None | None | N |
| V/E | 0.995 | likely_pathogenic | 0.9954 | pathogenic | -2.991 | Highly Destabilizing | 0.999 | D | 0.891 | deleterious | None | None | None | None | N |
| V/F | 0.9184 | likely_pathogenic | 0.9369 | pathogenic | -1.399 | Destabilizing | 0.997 | D | 0.856 | deleterious | D | 0.560911414 | None | None | N |
| V/G | 0.965 | likely_pathogenic | 0.9693 | pathogenic | -3.058 | Highly Destabilizing | 0.999 | D | 0.891 | deleterious | D | 0.561164904 | None | None | N |
| V/H | 0.9988 | likely_pathogenic | 0.9989 | pathogenic | -2.945 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| V/I | 0.0861 | likely_benign | 0.094 | benign | -0.67 | Destabilizing | 0.428 | N | 0.289 | neutral | N | 0.449413866 | None | None | N |
| V/K | 0.9961 | likely_pathogenic | 0.9961 | pathogenic | -1.931 | Destabilizing | 0.998 | D | 0.891 | deleterious | None | None | None | None | N |
| V/L | 0.5244 | ambiguous | 0.5834 | pathogenic | -0.67 | Destabilizing | 0.957 | D | 0.621 | neutral | D | 0.530341739 | None | None | N |
| V/M | 0.7091 | likely_pathogenic | 0.7533 | pathogenic | -0.925 | Destabilizing | 0.998 | D | 0.79 | deleterious | None | None | None | None | N |
| V/N | 0.9966 | likely_pathogenic | 0.9969 | pathogenic | -2.729 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| V/P | 0.9874 | likely_pathogenic | 0.9884 | pathogenic | -1.252 | Destabilizing | 0.999 | D | 0.895 | deleterious | None | None | None | None | N |
| V/Q | 0.9947 | likely_pathogenic | 0.9952 | pathogenic | -2.3 | Highly Destabilizing | 0.999 | D | 0.909 | deleterious | None | None | None | None | N |
| V/R | 0.9921 | likely_pathogenic | 0.9921 | pathogenic | -2.162 | Highly Destabilizing | 0.999 | D | 0.905 | deleterious | None | None | None | None | N |
| V/S | 0.9762 | likely_pathogenic | 0.9805 | pathogenic | -3.139 | Highly Destabilizing | 0.998 | D | 0.894 | deleterious | None | None | None | None | N |
| V/T | 0.8505 | likely_pathogenic | 0.8685 | pathogenic | -2.641 | Highly Destabilizing | 0.983 | D | 0.719 | prob.delet. | None | None | None | None | N |
| V/W | 0.9987 | likely_pathogenic | 0.9992 | pathogenic | -1.857 | Destabilizing | 1.0 | D | 0.87 | deleterious | None | None | None | None | N |
| V/Y | 0.9957 | likely_pathogenic | 0.9966 | pathogenic | -1.638 | Destabilizing | 0.999 | D | 0.864 | 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.