Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29447 | 88564;88565;88566 | chr2:178555120;178555119;178555118 | chr2:179419847;179419846;179419845 |
| N2AB | 27806 | 83641;83642;83643 | chr2:178555120;178555119;178555118 | chr2:179419847;179419846;179419845 |
| N2A | 26879 | 80860;80861;80862 | chr2:178555120;178555119;178555118 | chr2:179419847;179419846;179419845 |
| N2B | 20382 | 61369;61370;61371 | chr2:178555120;178555119;178555118 | chr2:179419847;179419846;179419845 |
| Novex-1 | 20507 | 61744;61745;61746 | chr2:178555120;178555119;178555118 | chr2:179419847;179419846;179419845 |
| Novex-2 | 20574 | 61945;61946;61947 | chr2:178555120;178555119;178555118 | chr2:179419847;179419846;179419845 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs140201636  |
0.117 | None | N | 0.247 | 0.105 | 0.232513804876 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.29E-05 | None | 0 | 0 | 0 |
| T/I | rs140201636 |
0.117 | None | N | 0.247 | 0.105 | 0.232513804876 | gnomAD-4.0.0 | 6.84447E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16236E-05 | 0 |
| T/K | None | None | 0.211 | N | 0.392 | 0.216 | 0.244539031024 | gnomAD-4.0.0 | 6.84447E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65678E-05 |
| T/R | rs140201636 |
-0.119 | 0.484 | N | 0.4 | 0.273 | None | gnomAD-2.1.1 | 2.29865E-04 | None | None | None | None | N | None | 2.56899E-03 | 0 | None | 0 | 5.14E-05 | None | 0 | None | 0 | 0 | 1.40924E-04 |
| T/R | rs140201636 |
-0.119 | 0.484 | N | 0.4 | 0.273 | None | gnomAD-3.1.2 | 7.82709E-04 | None | None | None | None | N | None | 2.70571E-03 | 4.58535E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/R | rs140201636 |
-0.119 | 0.484 | N | 0.4 | 0.273 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | N | None | 2.3E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/R | rs140201636 |
-0.119 | 0.484 | N | 0.4 | 0.273 | None | gnomAD-4.0.0 | 1.37616E-04 | None | None | None | None | N | None | 2.74762E-03 | 1.5018E-04 | None | 0 | 2.23025E-05 | None | 0 | 0 | 1.69539E-06 | 0 | 6.40369E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0792 | likely_benign | 0.0691 | benign | -0.209 | Destabilizing | 0.052 | N | 0.324 | neutral | N | 0.396526318 | None | None | N |
| T/C | 0.3727 | ambiguous | 0.3462 | ambiguous | -0.392 | Destabilizing | 0.935 | D | 0.366 | neutral | None | None | None | None | N |
| T/D | 0.3567 | ambiguous | 0.3079 | benign | 0.173 | Stabilizing | 0.555 | D | 0.4 | neutral | None | None | None | None | N |
| T/E | 0.2392 | likely_benign | 0.2066 | benign | 0.088 | Stabilizing | 0.555 | D | 0.409 | neutral | None | None | None | None | N |
| T/F | 0.3498 | ambiguous | 0.2851 | benign | -0.845 | Destabilizing | 0.001 | N | 0.384 | neutral | None | None | None | None | N |
| T/G | 0.1945 | likely_benign | 0.1721 | benign | -0.283 | Destabilizing | 0.262 | N | 0.396 | neutral | None | None | None | None | N |
| T/H | 0.226 | likely_benign | 0.2068 | benign | -0.461 | Destabilizing | 0.935 | D | 0.415 | neutral | None | None | None | None | N |
| T/I | 0.2176 | likely_benign | 0.1614 | benign | -0.14 | Destabilizing | None | N | 0.247 | neutral | N | 0.444741552 | None | None | N |
| T/K | 0.1207 | likely_benign | 0.1068 | benign | -0.255 | Destabilizing | 0.211 | N | 0.392 | neutral | N | 0.38348245 | None | None | N |
| T/L | 0.0995 | likely_benign | 0.0866 | benign | -0.14 | Destabilizing | None | N | 0.206 | neutral | None | None | None | None | N |
| T/M | 0.1003 | likely_benign | 0.091 | benign | -0.166 | Destabilizing | 0.38 | N | 0.397 | neutral | None | None | None | None | N |
| T/N | 0.1257 | likely_benign | 0.1159 | benign | -0.105 | Destabilizing | 0.791 | D | 0.396 | neutral | None | None | None | None | N |
| T/P | 0.1539 | likely_benign | 0.1314 | benign | -0.138 | Destabilizing | 0.741 | D | 0.396 | neutral | N | 0.312545071 | None | None | N |
| T/Q | 0.1653 | likely_benign | 0.1554 | benign | -0.296 | Destabilizing | 0.791 | D | 0.397 | neutral | None | None | None | None | N |
| T/R | 0.102 | likely_benign | 0.0859 | benign | 0.014 | Stabilizing | 0.484 | N | 0.4 | neutral | N | 0.3665902 | None | None | N |
| T/S | 0.1035 | likely_benign | 0.0987 | benign | -0.287 | Destabilizing | 0.211 | N | 0.359 | neutral | N | 0.426675867 | None | None | N |
| T/V | 0.1585 | likely_benign | 0.1263 | benign | -0.138 | Destabilizing | 0.012 | N | 0.265 | neutral | None | None | None | None | N |
| T/W | 0.5805 | likely_pathogenic | 0.5197 | ambiguous | -0.912 | Destabilizing | 0.935 | D | 0.433 | neutral | None | None | None | None | N |
| T/Y | 0.3157 | likely_benign | 0.2864 | benign | -0.59 | Destabilizing | 0.235 | N | 0.441 | 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.