Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29713 | 89362;89363;89364 | chr2:178553974;178553973;178553972 | chr2:179418701;179418700;179418699 |
| N2AB | 28072 | 84439;84440;84441 | chr2:178553974;178553973;178553972 | chr2:179418701;179418700;179418699 |
| N2A | 27145 | 81658;81659;81660 | chr2:178553974;178553973;178553972 | chr2:179418701;179418700;179418699 |
| N2B | 20648 | 62167;62168;62169 | chr2:178553974;178553973;178553972 | chr2:179418701;179418700;179418699 |
| Novex-1 | 20773 | 62542;62543;62544 | chr2:178553974;178553973;178553972 | chr2:179418701;179418700;179418699 |
| Novex-2 | 20840 | 62743;62744;62745 | chr2:178553974;178553973;178553972 | chr2:179418701;179418700;179418699 |
| 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/T | rs1199888872  |
-0.183 | 0.998 | N | 0.415 | 0.201 | 0.404870348458 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| A/T | rs1199888872 |
-0.183 | 0.998 | N | 0.415 | 0.201 | 0.404870348458 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs1199888872 |
-0.183 | 0.998 | N | 0.415 | 0.201 | 0.404870348458 | gnomAD-4.0.0 | 9.92656E-06 | None | None | None | None | I | None | 2.6703E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32494E-06 | 1.09941E-05 | 3.20349E-05 |
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 | 0.5284 | ambiguous | 0.594 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.402 | neutral | None | None | None | None | I |
| A/D | 0.4158 | ambiguous | 0.4894 | ambiguous | -0.362 | Destabilizing | 0.997 | D | 0.529 | neutral | N | 0.520577744 | None | None | I |
| A/E | 0.3233 | likely_benign | 0.3816 | ambiguous | -0.515 | Destabilizing | 0.983 | D | 0.461 | neutral | None | None | None | None | I |
| A/F | 0.3979 | ambiguous | 0.4489 | ambiguous | -0.861 | Destabilizing | 0.999 | D | 0.584 | neutral | None | None | None | None | I |
| A/G | 0.2127 | likely_benign | 0.2406 | benign | -0.197 | Destabilizing | 0.989 | D | 0.402 | neutral | N | 0.470462823 | None | None | I |
| A/H | 0.5021 | ambiguous | 0.5648 | pathogenic | -0.191 | Destabilizing | 1.0 | D | 0.57 | neutral | None | None | None | None | I |
| A/I | 0.2137 | likely_benign | 0.2546 | benign | -0.366 | Destabilizing | 0.999 | D | 0.463 | neutral | None | None | None | None | I |
| A/K | 0.4582 | ambiguous | 0.492 | ambiguous | -0.408 | Destabilizing | 0.246 | N | 0.33 | neutral | None | None | None | None | I |
| A/L | 0.1424 | likely_benign | 0.1705 | benign | -0.366 | Destabilizing | 0.992 | D | 0.461 | neutral | None | None | None | None | I |
| A/M | 0.1889 | likely_benign | 0.2238 | benign | -0.427 | Destabilizing | 1.0 | D | 0.445 | neutral | None | None | None | None | I |
| A/N | 0.2727 | likely_benign | 0.334 | benign | -0.207 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | I |
| A/P | 0.6422 | likely_pathogenic | 0.7341 | pathogenic | -0.28 | Destabilizing | 1.0 | D | 0.471 | neutral | N | 0.478827977 | None | None | I |
| A/Q | 0.3409 | ambiguous | 0.382 | ambiguous | -0.475 | Destabilizing | 0.995 | D | 0.473 | neutral | None | None | None | None | I |
| A/R | 0.4635 | ambiguous | 0.4776 | ambiguous | 0.009 | Stabilizing | 0.967 | D | 0.452 | neutral | None | None | None | None | I |
| A/S | 0.1149 | likely_benign | 0.1272 | benign | -0.4 | Destabilizing | 0.991 | D | 0.421 | neutral | N | 0.478019046 | None | None | I |
| A/T | 0.0992 | likely_benign | 0.1123 | benign | -0.476 | Destabilizing | 0.998 | D | 0.415 | neutral | N | 0.467810386 | None | None | I |
| A/V | 0.1181 | likely_benign | 0.1331 | benign | -0.28 | Destabilizing | 0.989 | D | 0.427 | neutral | N | 0.514094489 | None | None | I |
| A/W | 0.8276 | likely_pathogenic | 0.8637 | pathogenic | -0.96 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| A/Y | 0.5144 | ambiguous | 0.5761 | pathogenic | -0.625 | Destabilizing | 0.999 | D | 0.581 | 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.