Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29304 | 88135;88136;88137 | chr2:178557352;178557351;178557350 | chr2:179422079;179422078;179422077 |
| N2AB | 27663 | 83212;83213;83214 | chr2:178557352;178557351;178557350 | chr2:179422079;179422078;179422077 |
| N2A | 26736 | 80431;80432;80433 | chr2:178557352;178557351;178557350 | chr2:179422079;179422078;179422077 |
| N2B | 20239 | 60940;60941;60942 | chr2:178557352;178557351;178557350 | chr2:179422079;179422078;179422077 |
| Novex-1 | 20364 | 61315;61316;61317 | chr2:178557352;178557351;178557350 | chr2:179422079;179422078;179422077 |
| Novex-2 | 20431 | 61516;61517;61518 | chr2:178557352;178557351;178557350 | chr2:179422079;179422078;179422077 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | rs571668367  |
-0.297 | 0.999 | N | 0.709 | 0.243 | 0.191931220699 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/P | rs571668367 |
-0.297 | 0.999 | N | 0.709 | 0.243 | 0.191931220699 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| A/P | rs571668367 |
-0.297 | 0.999 | N | 0.709 | 0.243 | 0.191931220699 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| A/P | rs571668367 |
-0.297 | 0.999 | N | 0.709 | 0.243 | 0.191931220699 | gnomAD-4.0.0 | 1.23919E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.09789E-05 | 1.60036E-05 |
| A/T | rs571668367 |
-0.712 | 0.992 | N | 0.655 | 0.287 | 0.264547087235 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| A/T | rs571668367 |
-0.712 | 0.992 | N | 0.655 | 0.287 | 0.264547087235 | gnomAD-4.0.0 | 2.05247E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69825E-06 | 0 | 0 |
| A/V | None | None | 0.998 | N | 0.676 | 0.391 | 0.461408135625 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.628 | likely_pathogenic | 0.6279 | pathogenic | -0.799 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| A/D | 0.679 | likely_pathogenic | 0.5815 | pathogenic | -0.12 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | N | 0.498069031 | None | None | N |
| A/E | 0.5048 | ambiguous | 0.4157 | ambiguous | -0.235 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| A/F | 0.7355 | likely_pathogenic | 0.7011 | pathogenic | -0.726 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| A/G | 0.2595 | likely_benign | 0.2321 | benign | -0.467 | Destabilizing | 0.996 | D | 0.529 | neutral | N | 0.475346887 | None | None | N |
| A/H | 0.7298 | likely_pathogenic | 0.6945 | pathogenic | -0.388 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| A/I | 0.5936 | likely_pathogenic | 0.5532 | ambiguous | -0.254 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | None | None | None | None | N |
| A/K | 0.7716 | likely_pathogenic | 0.7424 | pathogenic | -0.649 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/L | 0.4501 | ambiguous | 0.4117 | ambiguous | -0.254 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| A/M | 0.4891 | ambiguous | 0.4472 | ambiguous | -0.416 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| A/N | 0.504 | ambiguous | 0.4343 | ambiguous | -0.39 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| A/P | 0.1727 | likely_benign | 0.159 | benign | -0.252 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.360834011 | None | None | N |
| A/Q | 0.5143 | ambiguous | 0.4755 | ambiguous | -0.59 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| A/R | 0.7196 | likely_pathogenic | 0.6849 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| A/S | 0.1255 | likely_benign | 0.1134 | benign | -0.696 | Destabilizing | 0.957 | D | 0.345 | neutral | N | 0.449333722 | None | None | N |
| A/T | 0.1699 | likely_benign | 0.1524 | benign | -0.714 | Destabilizing | 0.992 | D | 0.655 | neutral | N | 0.454182181 | None | None | N |
| A/V | 0.3085 | likely_benign | 0.2705 | benign | -0.252 | Destabilizing | 0.998 | D | 0.676 | prob.neutral | N | 0.47948327 | None | None | N |
| A/W | 0.9292 | likely_pathogenic | 0.9241 | pathogenic | -0.901 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/Y | 0.7975 | likely_pathogenic | 0.7736 | pathogenic | -0.538 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | 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.