Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21561 | 64906;64907;64908 | chr2:178584960;178584959;178584958 | chr2:179449687;179449686;179449685 |
| N2AB | 19920 | 59983;59984;59985 | chr2:178584960;178584959;178584958 | chr2:179449687;179449686;179449685 |
| N2A | 18993 | 57202;57203;57204 | chr2:178584960;178584959;178584958 | chr2:179449687;179449686;179449685 |
| N2B | 12496 | 37711;37712;37713 | chr2:178584960;178584959;178584958 | chr2:179449687;179449686;179449685 |
| Novex-1 | 12621 | 38086;38087;38088 | chr2:178584960;178584959;178584958 | chr2:179449687;179449686;179449685 |
| Novex-2 | 12688 | 38287;38288;38289 | chr2:178584960;178584959;178584958 | chr2:179449687;179449686;179449685 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/S | rs200355808  |
-0.831 | 1.0 | N | 0.776 | 0.379 | None | gnomAD-2.1.1 | 4.67E-05 | None | None | None | None | N | None | 4.18E-05 | 0 | None | 0 | 2.06761E-04 | None | 9.84E-05 | None | 0 | 3.94E-05 | 0 |
| G/S | rs200355808 |
-0.831 | 1.0 | N | 0.776 | 0.379 | None | gnomAD-3.1.2 | 5.27E-05 | None | None | None | None | N | None | 7.25E-05 | 6.56E-05 | 0 | 0 | 3.88199E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| G/S | rs200355808 |
-0.831 | 1.0 | N | 0.776 | 0.379 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| G/S | rs200355808 |
-0.831 | 1.0 | N | 0.776 | 0.379 | None | gnomAD-4.0.0 | 3.78214E-05 | None | None | None | None | N | None | 8.00876E-05 | 1.66845E-05 | None | 0 | 1.3412E-04 | None | 0 | 0 | 3.73064E-05 | 3.29852E-05 | 1.60143E-05 |
| G/V | rs111829923 |
-0.277 | 1.0 | D | 0.82 | 0.528 | 0.554477701018 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.66E-05 | 1.79E-05 | 0 |
| G/V | rs111829923 |
-0.277 | 1.0 | D | 0.82 | 0.528 | 0.554477701018 | 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 |
| G/V | rs111829923 |
-0.277 | 1.0 | D | 0.82 | 0.528 | 0.554477701018 | gnomAD-4.0.0 | 1.17795E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52612E-05 | 0 | 1.60128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.3507 | ambiguous | 0.3215 | benign | -0.856 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.475950687 | None | None | N |
| G/C | 0.6954 | likely_pathogenic | 0.6861 | pathogenic | -1.278 | Destabilizing | 1.0 | D | 0.778 | deleterious | D | 0.525289929 | None | None | N |
| G/D | 0.8094 | likely_pathogenic | 0.8196 | pathogenic | -2.26 | Highly Destabilizing | 1.0 | D | 0.796 | deleterious | N | 0.512955552 | None | None | N |
| G/E | 0.8586 | likely_pathogenic | 0.8449 | pathogenic | -2.3 | Highly Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| G/F | 0.9472 | likely_pathogenic | 0.9394 | pathogenic | -1.219 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| G/H | 0.9396 | likely_pathogenic | 0.9445 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| G/I | 0.9189 | likely_pathogenic | 0.9191 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| G/K | 0.9575 | likely_pathogenic | 0.9595 | pathogenic | -1.38 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| G/L | 0.8618 | likely_pathogenic | 0.8444 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| G/M | 0.9114 | likely_pathogenic | 0.8995 | pathogenic | -0.458 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| G/N | 0.8387 | likely_pathogenic | 0.8216 | pathogenic | -1.262 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| G/P | 0.9944 | likely_pathogenic | 0.9953 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| G/Q | 0.9003 | likely_pathogenic | 0.8877 | pathogenic | -1.499 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| G/R | 0.9283 | likely_pathogenic | 0.931 | pathogenic | -1.027 | Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.489788981 | None | None | N |
| G/S | 0.2317 | likely_benign | 0.2324 | benign | -1.407 | Destabilizing | 1.0 | D | 0.776 | deleterious | N | 0.476107909 | None | None | N |
| G/T | 0.6249 | likely_pathogenic | 0.6491 | pathogenic | -1.389 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| G/V | 0.8504 | likely_pathogenic | 0.8519 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.82 | deleterious | D | 0.52503644 | None | None | N |
| G/W | 0.9426 | likely_pathogenic | 0.9434 | pathogenic | -1.594 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| G/Y | 0.9284 | likely_pathogenic | 0.9237 | pathogenic | -1.185 | Destabilizing | 1.0 | D | 0.801 | 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.