Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18422 | 55489;55490;55491 | chr2:178602007;178602006;178602005 | chr2:179466734;179466733;179466732 |
| N2AB | 16781 | 50566;50567;50568 | chr2:178602007;178602006;178602005 | chr2:179466734;179466733;179466732 |
| N2A | 15854 | 47785;47786;47787 | chr2:178602007;178602006;178602005 | chr2:179466734;179466733;179466732 |
| N2B | 9357 | 28294;28295;28296 | chr2:178602007;178602006;178602005 | chr2:179466734;179466733;179466732 |
| Novex-1 | 9482 | 28669;28670;28671 | chr2:178602007;178602006;178602005 | chr2:179466734;179466733;179466732 |
| Novex-2 | 9549 | 28870;28871;28872 | chr2:178602007;178602006;178602005 | chr2:179466734;179466733;179466732 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | rs1335806402  |
0.522 | None | N | 0.159 | 0.173 | 0.285698343383 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| M/K | rs1335806402 |
0.522 | None | N | 0.159 | 0.173 | 0.285698343383 | gnomAD-4.0.0 | 3.18698E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86246E-06 | 0 | 3.02939E-05 |
| M/R | None | None | 0.007 | N | 0.358 | 0.139 | 0.342168650903 | gnomAD-4.0.0 | 1.59349E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1122 | likely_benign | 0.1192 | benign | -0.972 | Destabilizing | None | N | 0.16 | neutral | None | None | None | None | N |
| M/C | 0.4198 | ambiguous | 0.4272 | ambiguous | -0.705 | Destabilizing | 0.245 | N | 0.291 | neutral | None | None | None | None | N |
| M/D | 0.3937 | ambiguous | 0.4346 | ambiguous | -0.026 | Destabilizing | 0.037 | N | 0.407 | neutral | None | None | None | None | N |
| M/E | 0.1886 | likely_benign | 0.2043 | benign | -0.063 | Destabilizing | 0.018 | N | 0.307 | neutral | None | None | None | None | N |
| M/F | 0.1853 | likely_benign | 0.1937 | benign | -0.437 | Destabilizing | 0.009 | N | 0.275 | neutral | None | None | None | None | N |
| M/G | 0.1974 | likely_benign | 0.2144 | benign | -1.197 | Destabilizing | 0.009 | N | 0.355 | neutral | None | None | None | None | N |
| M/H | 0.2483 | likely_benign | 0.2604 | benign | -0.323 | Destabilizing | 0.497 | N | 0.319 | neutral | None | None | None | None | N |
| M/I | 0.1018 | likely_benign | 0.1017 | benign | -0.453 | Destabilizing | None | N | 0.14 | neutral | N | 0.408473242 | None | None | N |
| M/K | 0.0757 | likely_benign | 0.0772 | benign | 0.061 | Stabilizing | None | N | 0.159 | neutral | N | 0.292070146 | None | None | N |
| M/L | 0.0866 | likely_benign | 0.0874 | benign | -0.453 | Destabilizing | None | N | 0.13 | neutral | N | 0.389887481 | None | None | N |
| M/N | 0.165 | likely_benign | 0.177 | benign | 0.246 | Stabilizing | 0.085 | N | 0.424 | neutral | None | None | None | None | N |
| M/P | 0.2082 | likely_benign | 0.2524 | benign | -0.598 | Destabilizing | 0.085 | N | 0.412 | neutral | None | None | None | None | N |
| M/Q | 0.1037 | likely_benign | 0.108 | benign | 0.071 | Stabilizing | 0.044 | N | 0.274 | neutral | None | None | None | None | N |
| M/R | 0.0972 | likely_benign | 0.1003 | benign | 0.59 | Stabilizing | 0.007 | N | 0.358 | neutral | N | 0.364586392 | None | None | N |
| M/S | 0.13 | likely_benign | 0.1374 | benign | -0.275 | Destabilizing | 0.004 | N | 0.279 | neutral | None | None | None | None | N |
| M/T | 0.0881 | likely_benign | 0.0901 | benign | -0.208 | Destabilizing | 0.003 | N | 0.263 | neutral | N | 0.34513384 | None | None | N |
| M/V | 0.0514 | likely_benign | 0.051 | benign | -0.598 | Destabilizing | None | N | 0.141 | neutral | N | 0.371301721 | None | None | N |
| M/W | 0.4484 | ambiguous | 0.4482 | ambiguous | -0.367 | Destabilizing | 0.497 | N | 0.291 | neutral | None | None | None | None | N |
| M/Y | 0.3652 | ambiguous | 0.3695 | ambiguous | -0.286 | Destabilizing | 0.085 | N | 0.38 | neutral | 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.