Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29129 | 87610;87611;87612 | chr2:178557969;178557968;178557967 | chr2:179422696;179422695;179422694 |
| N2AB | 27488 | 82687;82688;82689 | chr2:178557969;178557968;178557967 | chr2:179422696;179422695;179422694 |
| N2A | 26561 | 79906;79907;79908 | chr2:178557969;178557968;178557967 | chr2:179422696;179422695;179422694 |
| N2B | 20064 | 60415;60416;60417 | chr2:178557969;178557968;178557967 | chr2:179422696;179422695;179422694 |
| Novex-1 | 20189 | 60790;60791;60792 | chr2:178557969;178557968;178557967 | chr2:179422696;179422695;179422694 |
| Novex-2 | 20256 | 60991;60992;60993 | chr2:178557969;178557968;178557967 | chr2:179422696;179422695;179422694 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs1335641292  |
None | 0.004 | N | 0.217 | 0.198 | 0.435915822735 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| F/L | rs1335641292 |
None | 0.004 | N | 0.217 | 0.198 | 0.435915822735 | gnomAD-4.0.0 | 1.8596E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54264E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.221 | likely_benign | 0.232 | benign | -2.434 | Highly Destabilizing | 0.617 | D | 0.599 | neutral | None | None | None | None | N |
| F/C | 0.1627 | likely_benign | 0.175 | benign | -0.817 | Destabilizing | 0.99 | D | 0.608 | neutral | N | 0.5126442 | None | None | N |
| F/D | 0.3901 | ambiguous | 0.4234 | ambiguous | -1.736 | Destabilizing | 0.739 | D | 0.638 | neutral | None | None | None | None | N |
| F/E | 0.5183 | ambiguous | 0.534 | ambiguous | -1.693 | Destabilizing | 0.617 | D | 0.645 | neutral | None | None | None | None | N |
| F/G | 0.4691 | ambiguous | 0.4876 | ambiguous | -2.734 | Highly Destabilizing | 0.447 | N | 0.643 | neutral | None | None | None | None | N |
| F/H | 0.306 | likely_benign | 0.3129 | benign | -1.211 | Destabilizing | 0.012 | N | 0.372 | neutral | None | None | None | None | N |
| F/I | 0.1076 | likely_benign | 0.115 | benign | -1.522 | Destabilizing | 0.379 | N | 0.565 | neutral | N | 0.482321293 | None | None | N |
| F/K | 0.6047 | likely_pathogenic | 0.6263 | pathogenic | -1.303 | Destabilizing | 0.85 | D | 0.641 | neutral | None | None | None | None | N |
| F/L | 0.6056 | likely_pathogenic | 0.6304 | pathogenic | -1.522 | Destabilizing | 0.004 | N | 0.217 | neutral | N | 0.493269005 | None | None | N |
| F/M | 0.2786 | likely_benign | 0.2951 | benign | -0.9 | Destabilizing | 0.85 | D | 0.619 | neutral | None | None | None | None | N |
| F/N | 0.2545 | likely_benign | 0.2961 | benign | -1.206 | Destabilizing | 0.012 | N | 0.472 | neutral | None | None | None | None | N |
| F/P | 0.7907 | likely_pathogenic | 0.8119 | pathogenic | -1.822 | Destabilizing | 0.972 | D | 0.625 | neutral | None | None | None | None | N |
| F/Q | 0.4794 | ambiguous | 0.4859 | ambiguous | -1.394 | Destabilizing | 0.92 | D | 0.627 | neutral | None | None | None | None | N |
| F/R | 0.5134 | ambiguous | 0.5137 | ambiguous | -0.528 | Destabilizing | 0.85 | D | 0.637 | neutral | None | None | None | None | N |
| F/S | 0.1387 | likely_benign | 0.1476 | benign | -1.818 | Destabilizing | 0.379 | N | 0.641 | neutral | N | 0.456998774 | None | None | N |
| F/T | 0.1852 | likely_benign | 0.1925 | benign | -1.692 | Destabilizing | 0.617 | D | 0.639 | neutral | None | None | None | None | N |
| F/V | 0.0969 | likely_benign | 0.0985 | benign | -1.822 | Destabilizing | 0.379 | N | 0.565 | neutral | N | 0.463466173 | None | None | N |
| F/W | 0.3766 | ambiguous | 0.3848 | ambiguous | -1.01 | Destabilizing | 0.992 | D | 0.599 | neutral | None | None | None | None | N |
| F/Y | 0.1149 | likely_benign | 0.1162 | benign | -1.167 | Destabilizing | 0.016 | N | 0.293 | neutral | N | 0.482841368 | 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.