Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28867 | 86824;86825;86826 | chr2:178559533;178559532;178559531 | chr2:179424260;179424259;179424258 |
| N2AB | 27226 | 81901;81902;81903 | chr2:178559533;178559532;178559531 | chr2:179424260;179424259;179424258 |
| N2A | 26299 | 79120;79121;79122 | chr2:178559533;178559532;178559531 | chr2:179424260;179424259;179424258 |
| N2B | 19802 | 59629;59630;59631 | chr2:178559533;178559532;178559531 | chr2:179424260;179424259;179424258 |
| Novex-1 | 19927 | 60004;60005;60006 | chr2:178559533;178559532;178559531 | chr2:179424260;179424259;179424258 |
| Novex-2 | 19994 | 60205;60206;60207 | chr2:178559533;178559532;178559531 | chr2:179424260;179424259;179424258 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs757623132  |
-0.693 | 0.77 | N | 0.563 | 0.276 | 0.199424873507 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| D/G | rs757623132 |
-0.693 | 0.77 | N | 0.563 | 0.276 | 0.199424873507 | gnomAD-4.0.0 | 6.8422E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| D/V | None | None | 0.911 | N | 0.741 | 0.317 | 0.520427616228 | gnomAD-4.0.0 | 1.36844E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31895E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1579 | likely_benign | 0.1312 | benign | -0.453 | Destabilizing | 0.028 | N | 0.412 | neutral | N | 0.4977596 | None | None | N |
| D/C | 0.6079 | likely_pathogenic | 0.5208 | ambiguous | -0.208 | Destabilizing | 0.99 | D | 0.761 | deleterious | None | None | None | None | N |
| D/E | 0.1224 | likely_benign | 0.1119 | benign | -0.776 | Destabilizing | 0.003 | N | 0.261 | neutral | N | 0.463009521 | None | None | N |
| D/F | 0.6215 | likely_pathogenic | 0.5655 | pathogenic | -0.079 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | N |
| D/G | 0.1747 | likely_benign | 0.1359 | benign | -0.808 | Destabilizing | 0.77 | D | 0.563 | neutral | N | 0.501242622 | None | None | N |
| D/H | 0.3456 | ambiguous | 0.2818 | benign | -0.393 | Destabilizing | 0.997 | D | 0.725 | prob.delet. | N | 0.4729654 | None | None | N |
| D/I | 0.4077 | ambiguous | 0.3619 | ambiguous | 0.484 | Stabilizing | 0.994 | D | 0.777 | deleterious | None | None | None | None | N |
| D/K | 0.4279 | ambiguous | 0.3524 | ambiguous | -0.4 | Destabilizing | 0.987 | D | 0.73 | prob.delet. | None | None | None | None | N |
| D/L | 0.3981 | ambiguous | 0.3421 | ambiguous | 0.484 | Stabilizing | 0.987 | D | 0.77 | deleterious | None | None | None | None | N |
| D/M | 0.5039 | ambiguous | 0.4515 | ambiguous | 0.891 | Stabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| D/N | 0.1034 | likely_benign | 0.0905 | benign | -0.868 | Destabilizing | 0.935 | D | 0.567 | neutral | N | 0.483771582 | None | None | N |
| D/P | 0.9471 | likely_pathogenic | 0.9277 | pathogenic | 0.198 | Stabilizing | 0.86 | D | 0.757 | deleterious | None | None | None | None | N |
| D/Q | 0.3364 | likely_benign | 0.2804 | benign | -0.708 | Destabilizing | 0.966 | D | 0.619 | neutral | None | None | None | None | N |
| D/R | 0.4954 | ambiguous | 0.4033 | ambiguous | -0.217 | Destabilizing | 0.994 | D | 0.761 | deleterious | None | None | None | None | N |
| D/S | 0.1265 | likely_benign | 0.1076 | benign | -1.087 | Destabilizing | 0.86 | D | 0.436 | neutral | None | None | None | None | N |
| D/T | 0.2283 | likely_benign | 0.1955 | benign | -0.796 | Destabilizing | 0.95 | D | 0.727 | prob.delet. | None | None | None | None | N |
| D/V | 0.2397 | likely_benign | 0.2057 | benign | 0.198 | Stabilizing | 0.911 | D | 0.741 | deleterious | N | 0.511843618 | None | None | N |
| D/W | 0.8957 | likely_pathogenic | 0.8626 | pathogenic | 0.067 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/Y | 0.284 | likely_benign | 0.2444 | benign | 0.147 | Stabilizing | 1.0 | D | 0.761 | deleterious | N | 0.514614564 | 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.