Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
| N2AB | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
| N2A | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
| N2B | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
| Novex-1 | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
| Novex-2 | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
| Novex-3 | 70 | 433;434;435 | chr2:178802225;178802224;178802223 | chr2:179666952;179666951;179666950 |
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 | 0.11 | N | 0.314 | 0.441 | 0.531389887418 | gnomAD-4.0.0 | 1.20036E-06 | None | None | None | -0.843(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31255E-06 | 0 | 0 |
| V/M | rs772248060  |
-1.227 | 1.0 | D | 0.755 | 0.647 | 0.717771820488 | gnomAD-2.1.1 | 4.77E-05 | None | None | None | -1.404(TCAP) | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 2.28639E-04 | None | 0 | 3.52E-05 | 0 |
| V/M | rs772248060 |
-1.227 | 1.0 | D | 0.755 | 0.647 | 0.717771820488 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | -1.404(TCAP) | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 8.82E-05 | 0 | 0 |
| V/M | rs772248060 |
-1.227 | 1.0 | D | 0.755 | 0.647 | 0.717771820488 | gnomAD-4.0.0 | 2.41631E-05 | None | None | None | -1.404(TCAP) | N | None | 2.66909E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.11862E-05 | 1.09789E-04 | 3.20072E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4927 | ambiguous | 0.5132 | ambiguous | -1.814 | Destabilizing | 0.11 | N | 0.314 | neutral | N | 0.49787921 | None | -0.843(TCAP) | N |
| V/C | 0.9836 | likely_pathogenic | 0.9859 | pathogenic | -2.167 | Highly Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | -1.587(TCAP) | N |
| V/D | 0.9815 | likely_pathogenic | 0.985 | pathogenic | -2.72 | Highly Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | -1.192(TCAP) | N |
| V/E | 0.9571 | likely_pathogenic | 0.9627 | pathogenic | -2.651 | Highly Destabilizing | 0.999 | D | 0.744 | deleterious | D | 0.78596096 | None | -1.388(TCAP) | N |
| V/F | 0.8435 | likely_pathogenic | 0.8961 | pathogenic | -1.474 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | -1.34(TCAP) | N |
| V/G | 0.7775 | likely_pathogenic | 0.8125 | pathogenic | -2.158 | Highly Destabilizing | 0.996 | D | 0.735 | prob.delet. | D | 0.750290419 | None | -0.696(TCAP) | N |
| V/H | 0.9948 | likely_pathogenic | 0.9959 | pathogenic | -1.594 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | -0.93(TCAP) | N |
| V/I | 0.1442 | likely_benign | 0.1532 | benign | -0.92 | Destabilizing | 0.352 | N | 0.55 | neutral | None | None | None | -1.352(TCAP) | N |
| V/K | 0.9803 | likely_pathogenic | 0.9817 | pathogenic | -1.577 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | -2.092(TCAP) | N |
| V/L | 0.6127 | likely_pathogenic | 0.6776 | pathogenic | -0.92 | Destabilizing | 0.943 | D | 0.557 | neutral | D | 0.52350246 | None | -1.352(TCAP) | N |
| V/M | 0.5696 | likely_pathogenic | 0.6434 | pathogenic | -1.155 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.712206873 | None | -1.404(TCAP) | N |
| V/N | 0.9461 | likely_pathogenic | 0.9554 | pathogenic | -1.764 | Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | -1.46(TCAP) | N |
| V/P | 0.9268 | likely_pathogenic | 0.9255 | pathogenic | -1.189 | Destabilizing | 0.999 | D | 0.779 | deleterious | None | None | None | -1.174(TCAP) | N |
| V/Q | 0.9702 | likely_pathogenic | 0.974 | pathogenic | -1.917 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | -1.557(TCAP) | N |
| V/R | 0.9715 | likely_pathogenic | 0.9742 | pathogenic | -1.117 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | -2.25(TCAP) | N |
| V/S | 0.8049 | likely_pathogenic | 0.8281 | pathogenic | -2.277 | Highly Destabilizing | 0.989 | D | 0.716 | prob.delet. | None | None | None | -1.192(TCAP) | N |
| V/T | 0.5897 | likely_pathogenic | 0.5897 | pathogenic | -2.093 | Highly Destabilizing | 0.955 | D | 0.613 | neutral | None | None | None | -1.408(TCAP) | N |
| V/W | 0.9983 | likely_pathogenic | 0.9989 | pathogenic | -1.709 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | -1.667(TCAP) | N |
| V/Y | 0.9908 | likely_pathogenic | 0.9942 | pathogenic | -1.373 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | -1.418(TCAP) | 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.