Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24623 | 74092;74093;74094 | chr2:178572265;178572264;178572263 | chr2:179436992;179436991;179436990 |
| N2AB | 22982 | 69169;69170;69171 | chr2:178572265;178572264;178572263 | chr2:179436992;179436991;179436990 |
| N2A | 22055 | 66388;66389;66390 | chr2:178572265;178572264;178572263 | chr2:179436992;179436991;179436990 |
| N2B | 15558 | 46897;46898;46899 | chr2:178572265;178572264;178572263 | chr2:179436992;179436991;179436990 |
| Novex-1 | 15683 | 47272;47273;47274 | chr2:178572265;178572264;178572263 | chr2:179436992;179436991;179436990 |
| Novex-2 | 15750 | 47473;47474;47475 | chr2:178572265;178572264;178572263 | chr2:179436992;179436991;179436990 |
| 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/L | rs559112722  |
None | 0.048 | N | 0.473 | 0.126 | 0.180583059064 | gnomAD-4.0.0 | 6.84451E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52627E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs746596254 |
-2.752 | 0.972 | N | 0.759 | 0.51 | 0.694772400809 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs746596254 |
-2.752 | 0.972 | N | 0.759 | 0.51 | 0.694772400809 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs746596254 |
-2.752 | 0.972 | N | 0.759 | 0.51 | 0.694772400809 | gnomAD-4.0.0 | 3.84786E-06 | None | None | None | None | N | None | 1.69635E-05 | 1.69635E-05 | None | 0 | 2.43309E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs559112722 |
-1.462 | 0.025 | N | 0.211 | 0.101 | 0.273503213844 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12183E-04 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs559112722 |
-1.462 | 0.025 | N | 0.211 | 0.101 | 0.273503213844 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93349E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs559112722 |
-1.462 | 0.025 | N | 0.211 | 0.101 | 0.273503213844 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| I/V | rs559112722 |
-1.462 | 0.025 | N | 0.211 | 0.101 | 0.273503213844 | gnomAD-4.0.0 | 3.09934E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.70481E-05 | None | 0 | 0 | 1.69565E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9169 | likely_pathogenic | 0.92 | pathogenic | -2.527 | Highly Destabilizing | 0.985 | D | 0.73 | prob.delet. | None | None | None | None | N |
| I/C | 0.9298 | likely_pathogenic | 0.9303 | pathogenic | -1.925 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| I/D | 0.9961 | likely_pathogenic | 0.9958 | pathogenic | -2.828 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| I/E | 0.9904 | likely_pathogenic | 0.9905 | pathogenic | -2.622 | Highly Destabilizing | 1.0 | D | 0.808 | deleterious | None | None | None | None | N |
| I/F | 0.6943 | likely_pathogenic | 0.6527 | pathogenic | -1.469 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | N |
| I/G | 0.9798 | likely_pathogenic | 0.9804 | pathogenic | -3.059 | Highly Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| I/H | 0.9914 | likely_pathogenic | 0.9905 | pathogenic | -2.523 | Highly Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| I/K | 0.9839 | likely_pathogenic | 0.9828 | pathogenic | -1.932 | Destabilizing | 1.0 | D | 0.807 | deleterious | N | 0.504249613 | None | None | N |
| I/L | 0.1804 | likely_benign | 0.1801 | benign | -1.0 | Destabilizing | 0.048 | N | 0.473 | neutral | N | 0.403568855 | None | None | N |
| I/M | 0.2476 | likely_benign | 0.2415 | benign | -1.053 | Destabilizing | 0.941 | D | 0.721 | prob.delet. | N | 0.49187935 | None | None | N |
| I/N | 0.9381 | likely_pathogenic | 0.9362 | pathogenic | -2.21 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/P | 0.9696 | likely_pathogenic | 0.9652 | pathogenic | -1.489 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| I/Q | 0.9858 | likely_pathogenic | 0.9852 | pathogenic | -2.097 | Highly Destabilizing | 1.0 | D | 0.81 | deleterious | None | None | None | None | N |
| I/R | 0.982 | likely_pathogenic | 0.98 | pathogenic | -1.641 | Destabilizing | 1.0 | D | 0.804 | deleterious | N | 0.492893308 | None | None | N |
| I/S | 0.9577 | likely_pathogenic | 0.9586 | pathogenic | -2.902 | Highly Destabilizing | 0.999 | D | 0.763 | deleterious | None | None | None | None | N |
| I/T | 0.9258 | likely_pathogenic | 0.932 | pathogenic | -2.555 | Highly Destabilizing | 0.972 | D | 0.759 | deleterious | N | 0.492386329 | None | None | N |
| I/V | 0.1192 | likely_benign | 0.1185 | benign | -1.489 | Destabilizing | 0.025 | N | 0.211 | neutral | N | 0.401496916 | None | None | N |
| I/W | 0.9902 | likely_pathogenic | 0.988 | pathogenic | -1.855 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| I/Y | 0.9536 | likely_pathogenic | 0.9476 | pathogenic | -1.582 | Destabilizing | 0.994 | D | 0.753 | 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.