Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28582 | 85969;85970;85971 | chr2:178560388;178560387;178560386 | chr2:179425115;179425114;179425113 |
| N2AB | 26941 | 81046;81047;81048 | chr2:178560388;178560387;178560386 | chr2:179425115;179425114;179425113 |
| N2A | 26014 | 78265;78266;78267 | chr2:178560388;178560387;178560386 | chr2:179425115;179425114;179425113 |
| N2B | 19517 | 58774;58775;58776 | chr2:178560388;178560387;178560386 | chr2:179425115;179425114;179425113 |
| Novex-1 | 19642 | 59149;59150;59151 | chr2:178560388;178560387;178560386 | chr2:179425115;179425114;179425113 |
| Novex-2 | 19709 | 59350;59351;59352 | chr2:178560388;178560387;178560386 | chr2:179425115;179425114;179425113 |
| 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/K | rs201688358  |
-1.782 | 1.0 | D | 0.887 | 0.642 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | I | None | 4.1336E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/K | rs201688358 |
-1.782 | 1.0 | D | 0.887 | 0.642 | None | gnomAD-3.1.2 | 1.24961E-04 | None | None | None | None | I | None | 4.5907E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/K | rs201688358 |
-1.782 | 1.0 | D | 0.887 | 0.642 | None | gnomAD-4.0.0 | 1.85931E-05 | None | None | None | None | I | None | 3.8741E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60149E-05 |
| I/T | None | None | 1.0 | D | 0.857 | 0.582 | 0.765291902356 | gnomAD-4.0.0 | 6.84252E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99463E-07 | 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 | 0.9658 | likely_pathogenic | 0.9437 | pathogenic | -2.226 | Highly Destabilizing | 0.999 | D | 0.672 | neutral | None | None | None | None | I |
| I/C | 0.9719 | likely_pathogenic | 0.9577 | pathogenic | -1.54 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | I |
| I/D | 0.9939 | likely_pathogenic | 0.9897 | pathogenic | -1.812 | Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | I |
| I/E | 0.9906 | likely_pathogenic | 0.9849 | pathogenic | -1.744 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | I |
| I/F | 0.8323 | likely_pathogenic | 0.768 | pathogenic | -1.555 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | I |
| I/G | 0.9924 | likely_pathogenic | 0.9847 | pathogenic | -2.636 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | I |
| I/H | 0.99 | likely_pathogenic | 0.9834 | pathogenic | -1.828 | Destabilizing | 1.0 | D | 0.863 | deleterious | None | None | None | None | I |
| I/K | 0.9807 | likely_pathogenic | 0.9687 | pathogenic | -1.521 | Destabilizing | 1.0 | D | 0.887 | deleterious | D | 0.545202426 | None | None | I |
| I/L | 0.4028 | ambiguous | 0.3314 | benign | -1.122 | Destabilizing | 0.993 | D | 0.443 | neutral | N | 0.490290096 | None | None | I |
| I/M | 0.5023 | ambiguous | 0.4316 | ambiguous | -0.922 | Destabilizing | 1.0 | D | 0.832 | deleterious | D | 0.544188468 | None | None | I |
| I/N | 0.8795 | likely_pathogenic | 0.8369 | pathogenic | -1.437 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | I |
| I/P | 0.957 | likely_pathogenic | 0.9454 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | I |
| I/Q | 0.9881 | likely_pathogenic | 0.9807 | pathogenic | -1.565 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | I |
| I/R | 0.9776 | likely_pathogenic | 0.964 | pathogenic | -0.956 | Destabilizing | 1.0 | D | 0.885 | deleterious | D | 0.563306681 | None | None | I |
| I/S | 0.9626 | likely_pathogenic | 0.9415 | pathogenic | -2.156 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | I |
| I/T | 0.938 | likely_pathogenic | 0.9062 | pathogenic | -1.958 | Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.528312712 | None | None | I |
| I/V | 0.17 | likely_benign | 0.141 | benign | -1.462 | Destabilizing | 0.993 | D | 0.413 | neutral | N | 0.509056816 | None | None | I |
| I/W | 0.9947 | likely_pathogenic | 0.9911 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| I/Y | 0.9595 | likely_pathogenic | 0.9404 | pathogenic | -1.452 | Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | I |
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.