Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29245 | 87958;87959;87960 | chr2:178557529;178557528;178557527 | chr2:179422256;179422255;179422254 |
| N2AB | 27604 | 83035;83036;83037 | chr2:178557529;178557528;178557527 | chr2:179422256;179422255;179422254 |
| N2A | 26677 | 80254;80255;80256 | chr2:178557529;178557528;178557527 | chr2:179422256;179422255;179422254 |
| N2B | 20180 | 60763;60764;60765 | chr2:178557529;178557528;178557527 | chr2:179422256;179422255;179422254 |
| Novex-1 | 20305 | 61138;61139;61140 | chr2:178557529;178557528;178557527 | chr2:179422256;179422255;179422254 |
| Novex-2 | 20372 | 61339;61340;61341 | chr2:178557529;178557528;178557527 | chr2:179422256;179422255;179422254 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/C | rs745430117  |
0.292 | 0.99 | N | 0.615 | 0.34 | 0.516491959214 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| W/C | rs745430117 |
0.292 | 0.99 | N | 0.615 | 0.34 | 0.516491959214 | gnomAD-4.0.0 | 1.59116E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85783E-06 | 0 | 0 |
| W/G | None | None | 0.549 | N | 0.558 | 0.26 | 0.442363741745 | gnomAD-4.0.0 | 4.80129E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25001E-06 | 0 | 0 |
| W/R | rs771722716 |
0.274 | 0.009 | N | 0.391 | 0.164 | 0.137902524267 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| W/R | rs771722716 |
0.274 | 0.009 | N | 0.391 | 0.164 | 0.137902524267 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| W/A | 0.444 | ambiguous | 0.4837 | ambiguous | -2.356 | Highly Destabilizing | 0.617 | D | 0.565 | neutral | None | None | None | None | I |
| W/C | 0.6431 | likely_pathogenic | 0.7083 | pathogenic | -0.703 | Destabilizing | 0.99 | D | 0.615 | neutral | N | 0.366176407 | None | None | I |
| W/D | 0.8095 | likely_pathogenic | 0.8283 | pathogenic | -1.138 | Destabilizing | 0.447 | N | 0.573 | neutral | None | None | None | None | I |
| W/E | 0.6952 | likely_pathogenic | 0.7231 | pathogenic | -1.084 | Destabilizing | 0.009 | N | 0.37 | neutral | None | None | None | None | I |
| W/F | 0.2257 | likely_benign | 0.2071 | benign | -1.399 | Destabilizing | 0.972 | D | 0.647 | neutral | None | None | None | None | I |
| W/G | 0.4656 | ambiguous | 0.5119 | ambiguous | -2.546 | Highly Destabilizing | 0.549 | D | 0.558 | neutral | N | 0.381009787 | None | None | I |
| W/H | 0.5832 | likely_pathogenic | 0.5853 | pathogenic | -1.078 | Destabilizing | 0.92 | D | 0.595 | neutral | None | None | None | None | I |
| W/I | 0.4589 | ambiguous | 0.4733 | ambiguous | -1.7 | Destabilizing | 0.92 | D | 0.592 | neutral | None | None | None | None | I |
| W/K | 0.7186 | likely_pathogenic | 0.745 | pathogenic | -1.131 | Destabilizing | 0.447 | N | 0.56 | neutral | None | None | None | None | I |
| W/L | 0.397 | ambiguous | 0.4335 | ambiguous | -1.7 | Destabilizing | 0.549 | D | 0.562 | neutral | N | 0.353881901 | None | None | I |
| W/M | 0.5112 | ambiguous | 0.521 | ambiguous | -1.132 | Destabilizing | 0.992 | D | 0.579 | neutral | None | None | None | None | I |
| W/N | 0.7624 | likely_pathogenic | 0.7505 | pathogenic | -1.455 | Destabilizing | 0.85 | D | 0.598 | neutral | None | None | None | None | I |
| W/P | 0.9878 | likely_pathogenic | 0.9915 | pathogenic | -1.929 | Destabilizing | 0.972 | D | 0.593 | neutral | None | None | None | None | I |
| W/Q | 0.6221 | likely_pathogenic | 0.6553 | pathogenic | -1.433 | Destabilizing | 0.85 | D | 0.575 | neutral | None | None | None | None | I |
| W/R | 0.6069 | likely_pathogenic | 0.6544 | pathogenic | -0.667 | Destabilizing | 0.009 | N | 0.391 | neutral | N | 0.278093276 | None | None | I |
| W/S | 0.3501 | ambiguous | 0.3655 | ambiguous | -1.793 | Destabilizing | 0.549 | D | 0.573 | neutral | N | 0.33721615 | None | None | I |
| W/T | 0.3911 | ambiguous | 0.4212 | ambiguous | -1.694 | Destabilizing | 0.617 | D | 0.581 | neutral | None | None | None | None | I |
| W/V | 0.3574 | ambiguous | 0.3852 | ambiguous | -1.929 | Destabilizing | 0.92 | D | 0.577 | neutral | None | None | None | None | I |
| W/Y | 0.3964 | ambiguous | 0.3833 | ambiguous | -1.358 | Destabilizing | 0.972 | D | 0.609 | 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.