Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21526 | 64801;64802;64803 | chr2:178585168;178585167;178585166 | chr2:179449895;179449894;179449893 |
| N2AB | 19885 | 59878;59879;59880 | chr2:178585168;178585167;178585166 | chr2:179449895;179449894;179449893 |
| N2A | 18958 | 57097;57098;57099 | chr2:178585168;178585167;178585166 | chr2:179449895;179449894;179449893 |
| N2B | 12461 | 37606;37607;37608 | chr2:178585168;178585167;178585166 | chr2:179449895;179449894;179449893 |
| Novex-1 | 12586 | 37981;37982;37983 | chr2:178585168;178585167;178585166 | chr2:179449895;179449894;179449893 |
| Novex-2 | 12653 | 38182;38183;38184 | chr2:178585168;178585167;178585166 | chr2:179449895;179449894;179449893 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs776476433  |
-3.335 | 0.324 | D | 0.703 | 0.679 | 0.826635456628 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.7E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs776476433 |
-3.335 | 0.324 | D | 0.703 | 0.679 | 0.826635456628 | gnomAD-4.0.0 | 3.42188E-06 | None | None | None | None | N | None | 0 | 6.70871E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 2.3197E-05 | 0 |
| I/V | rs1160431016 |
-1.857 | 0.001 | D | 0.259 | 0.325 | 0.643445338908 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.97E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs1160431016 |
-1.857 | 0.001 | D | 0.259 | 0.325 | 0.643445338908 | gnomAD-4.0.0 | 1.59227E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76963E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9462 | likely_pathogenic | 0.9175 | pathogenic | -3.022 | Highly Destabilizing | 0.116 | N | 0.673 | neutral | None | None | None | None | N |
| I/C | 0.9263 | likely_pathogenic | 0.9067 | pathogenic | -2.3 | Highly Destabilizing | 0.981 | D | 0.793 | deleterious | None | None | None | None | N |
| I/D | 0.9976 | likely_pathogenic | 0.9954 | pathogenic | -3.907 | Highly Destabilizing | 0.932 | D | 0.867 | deleterious | None | None | None | None | N |
| I/E | 0.9915 | likely_pathogenic | 0.9849 | pathogenic | -3.633 | Highly Destabilizing | 0.818 | D | 0.849 | deleterious | None | None | None | None | N |
| I/F | 0.4542 | ambiguous | 0.4169 | ambiguous | -1.855 | Destabilizing | 0.527 | D | 0.684 | prob.neutral | None | None | None | None | N |
| I/G | 0.9892 | likely_pathogenic | 0.982 | pathogenic | -3.577 | Highly Destabilizing | 0.818 | D | 0.831 | deleterious | None | None | None | None | N |
| I/H | 0.9778 | likely_pathogenic | 0.9646 | pathogenic | -3.165 | Highly Destabilizing | 0.981 | D | 0.864 | deleterious | None | None | None | None | N |
| I/K | 0.9651 | likely_pathogenic | 0.9414 | pathogenic | -2.633 | Highly Destabilizing | 0.627 | D | 0.837 | deleterious | D | 0.628985387 | None | None | N |
| I/L | 0.2159 | likely_benign | 0.1921 | benign | -1.36 | Destabilizing | 0.001 | N | 0.301 | neutral | D | 0.538119721 | None | None | N |
| I/M | 0.2402 | likely_benign | 0.2257 | benign | -1.34 | Destabilizing | 0.041 | N | 0.465 | neutral | D | 0.602034645 | None | None | N |
| I/N | 0.9631 | likely_pathogenic | 0.9323 | pathogenic | -3.212 | Highly Destabilizing | 0.818 | D | 0.863 | deleterious | None | None | None | None | N |
| I/P | 0.9955 | likely_pathogenic | 0.9926 | pathogenic | -1.904 | Destabilizing | 0.932 | D | 0.866 | deleterious | None | None | None | None | N |
| I/Q | 0.9688 | likely_pathogenic | 0.9502 | pathogenic | -2.976 | Highly Destabilizing | 0.818 | D | 0.863 | deleterious | None | None | None | None | N |
| I/R | 0.9519 | likely_pathogenic | 0.9216 | pathogenic | -2.343 | Highly Destabilizing | 0.627 | D | 0.865 | deleterious | D | 0.612966026 | None | None | N |
| I/S | 0.9513 | likely_pathogenic | 0.9222 | pathogenic | -3.768 | Highly Destabilizing | 0.69 | D | 0.816 | deleterious | None | None | None | None | N |
| I/T | 0.9448 | likely_pathogenic | 0.91 | pathogenic | -3.358 | Highly Destabilizing | 0.324 | N | 0.703 | prob.neutral | D | 0.612562417 | None | None | N |
| I/V | 0.1653 | likely_benign | 0.1492 | benign | -1.904 | Destabilizing | 0.001 | N | 0.259 | neutral | D | 0.561386322 | None | None | N |
| I/W | 0.9689 | likely_pathogenic | 0.9621 | pathogenic | -2.39 | Highly Destabilizing | 0.981 | D | 0.86 | deleterious | None | None | None | None | N |
| I/Y | 0.9259 | likely_pathogenic | 0.9031 | pathogenic | -2.162 | Highly Destabilizing | 0.818 | D | 0.79 | 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.