Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23601 | 71026;71027;71028 | chr2:178575331;178575330;178575329 | chr2:179440058;179440057;179440056 |
| N2AB | 21960 | 66103;66104;66105 | chr2:178575331;178575330;178575329 | chr2:179440058;179440057;179440056 |
| N2A | 21033 | 63322;63323;63324 | chr2:178575331;178575330;178575329 | chr2:179440058;179440057;179440056 |
| N2B | 14536 | 43831;43832;43833 | chr2:178575331;178575330;178575329 | chr2:179440058;179440057;179440056 |
| Novex-1 | 14661 | 44206;44207;44208 | chr2:178575331;178575330;178575329 | chr2:179440058;179440057;179440056 |
| Novex-2 | 14728 | 44407;44408;44409 | chr2:178575331;178575330;178575329 | chr2:179440058;179440057;179440056 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1421650962  |
None | 1.0 | D | 0.869 | 0.841 | 0.889497162433 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| Y/C | rs1421650962 |
None | 1.0 | D | 0.869 | 0.841 | 0.889497162433 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| Y/C | rs1421650962 |
None | 1.0 | D | 0.869 | 0.841 | 0.889497162433 | gnomAD-4.0.0 | 7.10501E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.43477E-06 | 0 | 0 |
| Y/N | None | None | 1.0 | D | 0.863 | 0.851 | 0.919396666935 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | rs1421650962 |
None | 1.0 | D | 0.872 | 0.873 | 0.903639186133 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | rs1421650962 |
None | 1.0 | D | 0.872 | 0.873 | 0.903639186133 | gnomAD-4.0.0 | 6.5741E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.989 | likely_pathogenic | 0.9892 | pathogenic | -2.941 | Highly Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| Y/C | 0.8844 | likely_pathogenic | 0.8793 | pathogenic | -1.919 | Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.687562268 | None | None | N |
| Y/D | 0.9883 | likely_pathogenic | 0.9879 | pathogenic | -2.75 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | D | 0.687562268 | None | None | N |
| Y/E | 0.9963 | likely_pathogenic | 0.9963 | pathogenic | -2.546 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| Y/F | 0.2225 | likely_benign | 0.2335 | benign | -1.045 | Destabilizing | 0.999 | D | 0.755 | deleterious | D | 0.626311878 | None | None | N |
| Y/G | 0.9776 | likely_pathogenic | 0.9768 | pathogenic | -3.374 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| Y/H | 0.9325 | likely_pathogenic | 0.9309 | pathogenic | -1.873 | Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.671542907 | None | None | N |
| Y/I | 0.9171 | likely_pathogenic | 0.9246 | pathogenic | -1.524 | Destabilizing | 0.999 | D | 0.848 | deleterious | None | None | None | None | N |
| Y/K | 0.9956 | likely_pathogenic | 0.9956 | pathogenic | -2.034 | Highly Destabilizing | 1.0 | D | 0.866 | deleterious | None | None | None | None | N |
| Y/L | 0.8598 | likely_pathogenic | 0.8685 | pathogenic | -1.524 | Destabilizing | 0.997 | D | 0.812 | deleterious | None | None | None | None | N |
| Y/M | 0.9247 | likely_pathogenic | 0.9319 | pathogenic | -1.391 | Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | N |
| Y/N | 0.9288 | likely_pathogenic | 0.9301 | pathogenic | -2.745 | Highly Destabilizing | 1.0 | D | 0.863 | deleterious | D | 0.687360463 | None | None | N |
| Y/P | 0.9992 | likely_pathogenic | 0.9991 | pathogenic | -2.009 | Highly Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| Y/Q | 0.9943 | likely_pathogenic | 0.9943 | pathogenic | -2.491 | Highly Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | N |
| Y/R | 0.9908 | likely_pathogenic | 0.9901 | pathogenic | -1.805 | Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| Y/S | 0.9775 | likely_pathogenic | 0.9773 | pathogenic | -3.24 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | D | 0.687562268 | None | None | N |
| Y/T | 0.988 | likely_pathogenic | 0.988 | pathogenic | -2.91 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| Y/V | 0.8785 | likely_pathogenic | 0.8839 | pathogenic | -2.009 | Highly Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| Y/W | 0.7806 | likely_pathogenic | 0.7904 | pathogenic | -0.329 | Destabilizing | 1.0 | D | 0.829 | deleterious | 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.