Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19838 | 59737;59738;59739 | chr2:178592493;178592492;178592491 | chr2:179457220;179457219;179457218 |
| N2AB | 18197 | 54814;54815;54816 | chr2:178592493;178592492;178592491 | chr2:179457220;179457219;179457218 |
| N2A | 17270 | 52033;52034;52035 | chr2:178592493;178592492;178592491 | chr2:179457220;179457219;179457218 |
| N2B | 10773 | 32542;32543;32544 | chr2:178592493;178592492;178592491 | chr2:179457220;179457219;179457218 |
| Novex-1 | 10898 | 32917;32918;32919 | chr2:178592493;178592492;178592491 | chr2:179457220;179457219;179457218 |
| Novex-2 | 10965 | 33118;33119;33120 | chr2:178592493;178592492;178592491 | chr2:179457220;179457219;179457218 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.061 | N | 0.107 | 0.119 | 0.344483371355 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-06 | 0 | 0 |
| V/F | rs767665016  |
-0.715 | 0.996 | N | 0.253 | 0.327 | 0.717896021573 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/F | rs767665016 |
-0.715 | 0.996 | N | 0.253 | 0.327 | 0.717896021573 | gnomAD-4.0.0 | 6.84322E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99586E-07 | 0 | 0 |
| V/L | rs767665016 |
-0.182 | 0.826 | N | 0.291 | 0.219 | 0.31501682445 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65893E-04 |
| V/L | rs767665016 |
-0.182 | 0.826 | N | 0.291 | 0.219 | 0.31501682445 | gnomAD-4.0.0 | 4.10593E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.87301E-05 | 0 | 4.49793E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1624 | likely_benign | 0.1147 | benign | -0.679 | Destabilizing | 0.061 | N | 0.107 | neutral | N | 0.464890325 | None | None | N |
| V/C | 0.7708 | likely_pathogenic | 0.6881 | pathogenic | -0.796 | Destabilizing | 0.999 | D | 0.241 | neutral | None | None | None | None | N |
| V/D | 0.4565 | ambiguous | 0.315 | benign | -0.148 | Destabilizing | 0.92 | D | 0.32 | neutral | N | 0.403956509 | None | None | N |
| V/E | 0.4031 | ambiguous | 0.29 | benign | -0.184 | Destabilizing | 0.939 | D | 0.342 | neutral | None | None | None | None | N |
| V/F | 0.1993 | likely_benign | 0.1448 | benign | -0.523 | Destabilizing | 0.996 | D | 0.253 | neutral | N | 0.452731891 | None | None | N |
| V/G | 0.2594 | likely_benign | 0.1773 | benign | -0.894 | Destabilizing | 0.92 | D | 0.331 | neutral | N | 0.390336638 | None | None | N |
| V/H | 0.6178 | likely_pathogenic | 0.467 | ambiguous | -0.25 | Destabilizing | 0.999 | D | 0.265 | neutral | None | None | None | None | N |
| V/I | 0.0881 | likely_benign | 0.0785 | benign | -0.226 | Destabilizing | 0.826 | D | 0.279 | neutral | N | 0.487209824 | None | None | N |
| V/K | 0.4924 | ambiguous | 0.3652 | ambiguous | -0.608 | Destabilizing | 0.939 | D | 0.354 | neutral | None | None | None | None | N |
| V/L | 0.2475 | likely_benign | 0.1866 | benign | -0.226 | Destabilizing | 0.826 | D | 0.291 | neutral | N | 0.470970935 | None | None | N |
| V/M | 0.1874 | likely_benign | 0.1359 | benign | -0.455 | Destabilizing | 0.997 | D | 0.239 | neutral | None | None | None | None | N |
| V/N | 0.3557 | ambiguous | 0.2137 | benign | -0.534 | Destabilizing | 0.982 | D | 0.329 | neutral | None | None | None | None | N |
| V/P | 0.7481 | likely_pathogenic | 0.6948 | pathogenic | -0.342 | Destabilizing | 0.991 | D | 0.31 | neutral | None | None | None | None | N |
| V/Q | 0.4039 | ambiguous | 0.2904 | benign | -0.642 | Destabilizing | 0.991 | D | 0.299 | neutral | None | None | None | None | N |
| V/R | 0.3909 | ambiguous | 0.2937 | benign | -0.163 | Destabilizing | 0.991 | D | 0.32 | neutral | None | None | None | None | N |
| V/S | 0.2261 | likely_benign | 0.1426 | benign | -1.004 | Destabilizing | 0.373 | N | 0.229 | neutral | None | None | None | None | N |
| V/T | 0.1624 | likely_benign | 0.1168 | benign | -0.923 | Destabilizing | 0.079 | N | 0.113 | neutral | None | None | None | None | N |
| V/W | 0.7959 | likely_pathogenic | 0.7068 | pathogenic | -0.651 | Destabilizing | 0.999 | D | 0.307 | neutral | None | None | None | None | N |
| V/Y | 0.5809 | likely_pathogenic | 0.4527 | ambiguous | -0.357 | Destabilizing | 0.997 | D | 0.248 | 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.