Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27206 | 81841;81842;81843 | chr2:178564516;178564515;178564514 | chr2:179429243;179429242;179429241 |
| N2AB | 25565 | 76918;76919;76920 | chr2:178564516;178564515;178564514 | chr2:179429243;179429242;179429241 |
| N2A | 24638 | 74137;74138;74139 | chr2:178564516;178564515;178564514 | chr2:179429243;179429242;179429241 |
| N2B | 18141 | 54646;54647;54648 | chr2:178564516;178564515;178564514 | chr2:179429243;179429242;179429241 |
| Novex-1 | 18266 | 55021;55022;55023 | chr2:178564516;178564515;178564514 | chr2:179429243;179429242;179429241 |
| Novex-2 | 18333 | 55222;55223;55224 | chr2:178564516;178564515;178564514 | chr2:179429243;179429242;179429241 |
| 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/T | rs369868913  |
-2.929 | None | N | 0.591 | 0.144 | None | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 4.16E-05 | 5.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 7.92E-06 | 0 |
| I/T | rs369868913 |
-2.929 | None | N | 0.591 | 0.144 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs369868913 |
-2.929 | None | N | 0.591 | 0.144 | None | gnomAD-4.0.0 | 1.2402E-05 | None | None | None | None | N | None | 2.67108E-05 | 3.34135E-05 | None | 0 | 0 | None | 0 | 0 | 1.3567E-05 | 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 | 0.3923 | ambiguous | 0.3206 | benign | -2.479 | Highly Destabilizing | 0.035 | N | 0.693 | prob.neutral | None | None | None | None | N |
| I/C | 0.6985 | likely_pathogenic | 0.6258 | pathogenic | -1.85 | Destabilizing | 0.824 | D | 0.671 | neutral | None | None | None | None | N |
| I/D | 0.8757 | likely_pathogenic | 0.8302 | pathogenic | -2.546 | Highly Destabilizing | 0.38 | N | 0.709 | prob.delet. | None | None | None | None | N |
| I/E | 0.7889 | likely_pathogenic | 0.7485 | pathogenic | -2.344 | Highly Destabilizing | 0.38 | N | 0.711 | prob.delet. | None | None | None | None | N |
| I/F | 0.2282 | likely_benign | 0.181 | benign | -1.45 | Destabilizing | 0.317 | N | 0.723 | prob.delet. | N | 0.476697929 | None | None | N |
| I/G | 0.8398 | likely_pathogenic | 0.774 | pathogenic | -3.005 | Highly Destabilizing | 0.38 | N | 0.708 | prob.delet. | None | None | None | None | N |
| I/H | 0.6046 | likely_pathogenic | 0.5307 | ambiguous | -2.391 | Highly Destabilizing | 0.935 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/K | 0.6769 | likely_pathogenic | 0.6243 | pathogenic | -1.907 | Destabilizing | 0.38 | N | 0.707 | prob.neutral | None | None | None | None | N |
| I/L | 0.1061 | likely_benign | 0.088 | benign | -0.976 | Destabilizing | None | N | 0.235 | neutral | N | 0.519998954 | None | None | N |
| I/M | 0.1028 | likely_benign | 0.0928 | benign | -0.992 | Destabilizing | 0.317 | N | 0.687 | prob.neutral | N | 0.493093891 | None | None | N |
| I/N | 0.401 | ambiguous | 0.3474 | ambiguous | -2.158 | Highly Destabilizing | 0.317 | N | 0.708 | prob.delet. | N | 0.46488387 | None | None | N |
| I/P | 0.9869 | likely_pathogenic | 0.9797 | pathogenic | -1.456 | Destabilizing | 0.555 | D | 0.707 | prob.neutral | None | None | None | None | N |
| I/Q | 0.6279 | likely_pathogenic | 0.5655 | pathogenic | -2.058 | Highly Destabilizing | 0.555 | D | 0.712 | prob.delet. | None | None | None | None | N |
| I/R | 0.5869 | likely_pathogenic | 0.5132 | ambiguous | -1.582 | Destabilizing | 0.38 | N | 0.719 | prob.delet. | None | None | None | None | N |
| I/S | 0.3523 | ambiguous | 0.3103 | benign | -2.885 | Highly Destabilizing | 0.062 | N | 0.682 | prob.neutral | N | 0.47069354 | None | None | N |
| I/T | 0.1485 | likely_benign | 0.1256 | benign | -2.54 | Highly Destabilizing | None | N | 0.591 | neutral | N | 0.490292123 | None | None | N |
| I/V | 0.0672 | likely_benign | 0.0621 | benign | -1.456 | Destabilizing | None | N | 0.174 | neutral | N | 0.451928523 | None | None | N |
| I/W | 0.7865 | likely_pathogenic | 0.7018 | pathogenic | -1.781 | Destabilizing | 0.935 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/Y | 0.5793 | likely_pathogenic | 0.5164 | ambiguous | -1.508 | Destabilizing | 0.555 | D | 0.703 | prob.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.