Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29164 | 87715;87716;87717 | chr2:178557864;178557863;178557862 | chr2:179422591;179422590;179422589 |
| N2AB | 27523 | 82792;82793;82794 | chr2:178557864;178557863;178557862 | chr2:179422591;179422590;179422589 |
| N2A | 26596 | 80011;80012;80013 | chr2:178557864;178557863;178557862 | chr2:179422591;179422590;179422589 |
| N2B | 20099 | 60520;60521;60522 | chr2:178557864;178557863;178557862 | chr2:179422591;179422590;179422589 |
| Novex-1 | 20224 | 60895;60896;60897 | chr2:178557864;178557863;178557862 | chr2:179422591;179422590;179422589 |
| Novex-2 | 20291 | 61096;61097;61098 | chr2:178557864;178557863;178557862 | chr2:179422591;179422590;179422589 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1318040081  |
0.24 | 1.0 | N | 0.658 | 0.535 | 0.471456661759 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| Y/C | rs1318040081 |
0.24 | 1.0 | N | 0.658 | 0.535 | 0.471456661759 | gnomAD-4.0.0 | 1.59111E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6184 | likely_pathogenic | 0.6362 | pathogenic | -0.767 | Destabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | I |
| Y/C | 0.2622 | likely_benign | 0.2756 | benign | 0.082 | Stabilizing | 1.0 | D | 0.658 | neutral | N | 0.512306874 | None | None | I |
| Y/D | 0.257 | likely_benign | 0.2823 | benign | 0.955 | Stabilizing | 1.0 | D | 0.688 | prob.neutral | N | 0.442802033 | None | None | I |
| Y/E | 0.6235 | likely_pathogenic | 0.6666 | pathogenic | 0.934 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| Y/F | 0.1646 | likely_benign | 0.1562 | benign | -0.411 | Destabilizing | 0.999 | D | 0.488 | neutral | N | 0.498812819 | None | None | I |
| Y/G | 0.5167 | ambiguous | 0.5415 | ambiguous | -0.953 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| Y/H | 0.3131 | likely_benign | 0.3475 | ambiguous | 0.161 | Stabilizing | 1.0 | D | 0.647 | neutral | N | 0.498986177 | None | None | I |
| Y/I | 0.6389 | likely_pathogenic | 0.6052 | pathogenic | -0.302 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| Y/K | 0.7106 | likely_pathogenic | 0.7613 | pathogenic | 0.181 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| Y/L | 0.5929 | likely_pathogenic | 0.569 | pathogenic | -0.302 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | None | I |
| Y/M | 0.6697 | likely_pathogenic | 0.6574 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| Y/N | 0.1443 | likely_benign | 0.1478 | benign | 0.013 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | N | 0.511683328 | None | None | I |
| Y/P | 0.9657 | likely_pathogenic | 0.9652 | pathogenic | -0.437 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | I |
| Y/Q | 0.5831 | likely_pathogenic | 0.6452 | pathogenic | 0.034 | Stabilizing | 1.0 | D | 0.702 | prob.neutral | None | None | None | None | I |
| Y/R | 0.6105 | likely_pathogenic | 0.6787 | pathogenic | 0.48 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| Y/S | 0.2797 | likely_benign | 0.297 | benign | -0.457 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.503602563 | None | None | I |
| Y/T | 0.4965 | ambiguous | 0.5053 | ambiguous | -0.389 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| Y/V | 0.5141 | ambiguous | 0.4989 | ambiguous | -0.437 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| Y/W | 0.6011 | likely_pathogenic | 0.6117 | pathogenic | -0.506 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
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.