Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29312 | 88159;88160;88161 | chr2:178557328;178557327;178557326 | chr2:179422055;179422054;179422053 |
| N2AB | 27671 | 83236;83237;83238 | chr2:178557328;178557327;178557326 | chr2:179422055;179422054;179422053 |
| N2A | 26744 | 80455;80456;80457 | chr2:178557328;178557327;178557326 | chr2:179422055;179422054;179422053 |
| N2B | 20247 | 60964;60965;60966 | chr2:178557328;178557327;178557326 | chr2:179422055;179422054;179422053 |
| Novex-1 | 20372 | 61339;61340;61341 | chr2:178557328;178557327;178557326 | chr2:179422055;179422054;179422053 |
| Novex-2 | 20439 | 61540;61541;61542 | chr2:178557328;178557327;178557326 | chr2:179422055;179422054;179422053 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs1436898678  |
-3.064 | 0.973 | D | 0.862 | 0.837 | 0.87712895824 | 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 |
| V/E | rs1436898678 |
-3.064 | 0.973 | D | 0.862 | 0.837 | 0.87712895824 | gnomAD-4.0.0 | 1.59102E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85775E-06 | 0 | 0 |
| V/M | rs751754225 |
-1.305 | 0.946 | D | 0.811 | 0.661 | 0.675724534598 | 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 |
| V/M | rs751754225 |
-1.305 | 0.946 | D | 0.811 | 0.661 | 0.675724534598 | gnomAD-4.0.0 | 3.18203E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71553E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7056 | likely_pathogenic | 0.6949 | pathogenic | -2.763 | Highly Destabilizing | 0.834 | D | 0.705 | prob.neutral | D | 0.546225244 | None | None | N |
| V/C | 0.9213 | likely_pathogenic | 0.9162 | pathogenic | -1.956 | Destabilizing | 0.998 | D | 0.805 | deleterious | None | None | None | None | N |
| V/D | 0.9977 | likely_pathogenic | 0.9976 | pathogenic | -3.306 | Highly Destabilizing | 0.979 | D | 0.89 | deleterious | None | None | None | None | N |
| V/E | 0.9944 | likely_pathogenic | 0.994 | pathogenic | -2.998 | Highly Destabilizing | 0.973 | D | 0.862 | deleterious | D | 0.640859734 | None | None | N |
| V/F | 0.9624 | likely_pathogenic | 0.9597 | pathogenic | -1.404 | Destabilizing | 0.959 | D | 0.822 | deleterious | None | None | None | None | N |
| V/G | 0.8721 | likely_pathogenic | 0.8685 | pathogenic | -3.315 | Highly Destabilizing | 0.973 | D | 0.876 | deleterious | D | 0.640859734 | None | None | N |
| V/H | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -2.947 | Highly Destabilizing | 0.998 | D | 0.861 | deleterious | None | None | None | None | N |
| V/I | 0.1422 | likely_benign | 0.1392 | benign | -1.122 | Destabilizing | 0.02 | N | 0.317 | neutral | None | None | None | None | N |
| V/K | 0.9974 | likely_pathogenic | 0.9973 | pathogenic | -2.019 | Highly Destabilizing | 0.979 | D | 0.865 | deleterious | None | None | None | None | N |
| V/L | 0.8045 | likely_pathogenic | 0.8022 | pathogenic | -1.122 | Destabilizing | 0.263 | N | 0.668 | neutral | D | 0.532294364 | None | None | N |
| V/M | 0.8462 | likely_pathogenic | 0.8472 | pathogenic | -1.461 | Destabilizing | 0.946 | D | 0.811 | deleterious | D | 0.553226683 | None | None | N |
| V/N | 0.9883 | likely_pathogenic | 0.987 | pathogenic | -2.661 | Highly Destabilizing | 0.993 | D | 0.889 | deleterious | None | None | None | None | N |
| V/P | 0.9949 | likely_pathogenic | 0.9953 | pathogenic | -1.657 | Destabilizing | 0.993 | D | 0.879 | deleterious | None | None | None | None | N |
| V/Q | 0.9941 | likely_pathogenic | 0.9934 | pathogenic | -2.299 | Highly Destabilizing | 0.993 | D | 0.885 | deleterious | None | None | None | None | N |
| V/R | 0.9937 | likely_pathogenic | 0.9932 | pathogenic | -2.084 | Highly Destabilizing | 0.979 | D | 0.892 | deleterious | None | None | None | None | N |
| V/S | 0.9154 | likely_pathogenic | 0.915 | pathogenic | -3.126 | Highly Destabilizing | 0.979 | D | 0.865 | deleterious | None | None | None | None | N |
| V/T | 0.7275 | likely_pathogenic | 0.7329 | pathogenic | -2.679 | Highly Destabilizing | 0.87 | D | 0.752 | deleterious | None | None | None | None | N |
| V/W | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -1.811 | Destabilizing | 0.998 | D | 0.841 | deleterious | None | None | None | None | N |
| V/Y | 0.9962 | likely_pathogenic | 0.9957 | pathogenic | -1.693 | Destabilizing | 0.979 | D | 0.833 | 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.