Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30895 | 92908;92909;92910 | chr2:178548943;178548942;178548941 | chr2:179413670;179413669;179413668 |
| N2AB | 29254 | 87985;87986;87987 | chr2:178548943;178548942;178548941 | chr2:179413670;179413669;179413668 |
| N2A | 28327 | 85204;85205;85206 | chr2:178548943;178548942;178548941 | chr2:179413670;179413669;179413668 |
| N2B | 21830 | 65713;65714;65715 | chr2:178548943;178548942;178548941 | chr2:179413670;179413669;179413668 |
| Novex-1 | 21955 | 66088;66089;66090 | chr2:178548943;178548942;178548941 | chr2:179413670;179413669;179413668 |
| Novex-2 | 22022 | 66289;66290;66291 | chr2:178548943;178548942;178548941 | chr2:179413670;179413669;179413668 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | rs200141081  |
-1.121 | 1.0 | D | 0.808 | 0.634 | 0.644857554221 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| R/P | rs200141081 |
-1.121 | 1.0 | D | 0.808 | 0.634 | 0.644857554221 | gnomAD-4.0.0 | 6.84178E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99437E-07 | 0 | 0 |
| R/Q | rs200141081 |
-1.091 | 1.0 | N | 0.786 | 0.414 | None | gnomAD-2.1.1 | 1.17785E-04 | None | None | None | None | N | None | 1.65344E-04 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.18692E-04 | 0 |
| R/Q | rs200141081 |
-1.091 | 1.0 | N | 0.786 | 0.414 | None | gnomAD-3.1.2 | 1.44577E-04 | None | None | None | None | N | None | 1.4476E-04 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.20478E-04 | 0 | 0 |
| R/Q | rs200141081 |
-1.091 | 1.0 | N | 0.786 | 0.414 | None | gnomAD-4.0.0 | 1.89617E-04 | None | None | None | None | N | None | 1.73518E-04 | 1.66711E-05 | None | 0 | 2.22787E-05 | None | 1.5626E-05 | 0 | 2.34778E-04 | 4.39136E-05 | 1.44083E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7976 | likely_pathogenic | 0.7186 | pathogenic | -1.715 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | N |
| R/C | 0.2027 | likely_benign | 0.1569 | benign | -1.804 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| R/D | 0.9842 | likely_pathogenic | 0.9707 | pathogenic | -0.802 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| R/E | 0.8218 | likely_pathogenic | 0.764 | pathogenic | -0.615 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/F | 0.8872 | likely_pathogenic | 0.8178 | pathogenic | -1.156 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| R/G | 0.8206 | likely_pathogenic | 0.7187 | pathogenic | -2.046 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.549614566 | None | None | N |
| R/H | 0.2361 | likely_benign | 0.1599 | benign | -2.025 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| R/I | 0.6028 | likely_pathogenic | 0.5364 | ambiguous | -0.776 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| R/K | 0.2333 | likely_benign | 0.1859 | benign | -1.426 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| R/L | 0.5819 | likely_pathogenic | 0.4696 | ambiguous | -0.776 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.512303192 | None | None | N |
| R/M | 0.6381 | likely_pathogenic | 0.555 | ambiguous | -1.262 | Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| R/N | 0.9228 | likely_pathogenic | 0.8778 | pathogenic | -1.2 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| R/P | 0.9975 | likely_pathogenic | 0.9952 | pathogenic | -1.075 | Destabilizing | 1.0 | D | 0.808 | deleterious | D | 0.549868055 | None | None | N |
| R/Q | 0.1627 | likely_benign | 0.1295 | benign | -1.158 | Destabilizing | 1.0 | D | 0.786 | deleterious | N | 0.475827966 | None | None | N |
| R/S | 0.8572 | likely_pathogenic | 0.7827 | pathogenic | -2.067 | Highly Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/T | 0.7153 | likely_pathogenic | 0.6175 | pathogenic | -1.68 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/V | 0.6655 | likely_pathogenic | 0.6136 | pathogenic | -1.075 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/W | 0.5064 | ambiguous | 0.3892 | ambiguous | -0.711 | Destabilizing | 1.0 | D | 0.782 | deleterious | None | None | None | None | N |
| R/Y | 0.7967 | likely_pathogenic | 0.6861 | pathogenic | -0.499 | Destabilizing | 1.0 | D | 0.837 | 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.