Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29367 | 88324;88325;88326 | chr2:178557055;178557054;178557053 | chr2:179421782;179421781;179421780 |
| N2AB | 27726 | 83401;83402;83403 | chr2:178557055;178557054;178557053 | chr2:179421782;179421781;179421780 |
| N2A | 26799 | 80620;80621;80622 | chr2:178557055;178557054;178557053 | chr2:179421782;179421781;179421780 |
| N2B | 20302 | 61129;61130;61131 | chr2:178557055;178557054;178557053 | chr2:179421782;179421781;179421780 |
| Novex-1 | 20427 | 61504;61505;61506 | chr2:178557055;178557054;178557053 | chr2:179421782;179421781;179421780 |
| Novex-2 | 20494 | 61705;61706;61707 | chr2:178557055;178557054;178557053 | chr2:179421782;179421781;179421780 |
| 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 | rs778882176  |
-2.159 | 0.722 | D | 0.812 | 0.472 | 0.714733430009 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/T | rs778882176 |
-2.159 | 0.722 | D | 0.812 | 0.472 | 0.714733430009 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs778882176 |
-2.159 | 0.722 | D | 0.812 | 0.472 | 0.714733430009 | gnomAD-4.0.0 | 5.12464E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17817E-06 | 0 | 2.84398E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9755 | likely_pathogenic | 0.9347 | pathogenic | -2.204 | Highly Destabilizing | 0.415 | N | 0.695 | prob.neutral | None | None | None | None | I |
| I/C | 0.9722 | likely_pathogenic | 0.935 | pathogenic | -1.497 | Destabilizing | 0.996 | D | 0.768 | deleterious | None | None | None | None | I |
| I/D | 0.9967 | likely_pathogenic | 0.9907 | pathogenic | -2.277 | Highly Destabilizing | 0.923 | D | 0.859 | deleterious | None | None | None | None | I |
| I/E | 0.9904 | likely_pathogenic | 0.9761 | pathogenic | -2.236 | Highly Destabilizing | 0.858 | D | 0.853 | deleterious | None | None | None | None | I |
| I/F | 0.8824 | likely_pathogenic | 0.7468 | pathogenic | -1.66 | Destabilizing | 0.901 | D | 0.681 | prob.neutral | D | 0.54593276 | None | None | I |
| I/G | 0.9942 | likely_pathogenic | 0.9826 | pathogenic | -2.583 | Highly Destabilizing | 0.923 | D | 0.856 | deleterious | None | None | None | None | I |
| I/H | 0.9913 | likely_pathogenic | 0.9733 | pathogenic | -1.858 | Destabilizing | 0.996 | D | 0.837 | deleterious | None | None | None | None | I |
| I/K | 0.9714 | likely_pathogenic | 0.9365 | pathogenic | -1.589 | Destabilizing | 0.011 | N | 0.563 | neutral | None | None | None | None | I |
| I/L | 0.3763 | ambiguous | 0.2477 | benign | -1.19 | Destabilizing | 0.349 | N | 0.497 | neutral | D | 0.524468985 | None | None | I |
| I/M | 0.4511 | ambiguous | 0.3127 | benign | -0.88 | Destabilizing | 0.901 | D | 0.637 | neutral | D | 0.541719706 | None | None | I |
| I/N | 0.9168 | likely_pathogenic | 0.8128 | pathogenic | -1.524 | Destabilizing | 0.901 | D | 0.861 | deleterious | D | 0.537960724 | None | None | I |
| I/P | 0.9635 | likely_pathogenic | 0.9119 | pathogenic | -1.501 | Destabilizing | 0.961 | D | 0.863 | deleterious | None | None | None | None | I |
| I/Q | 0.9823 | likely_pathogenic | 0.9538 | pathogenic | -1.703 | Destabilizing | 0.923 | D | 0.865 | deleterious | None | None | None | None | I |
| I/R | 0.9699 | likely_pathogenic | 0.9297 | pathogenic | -0.961 | Destabilizing | 0.858 | D | 0.853 | deleterious | None | None | None | None | I |
| I/S | 0.9748 | likely_pathogenic | 0.9344 | pathogenic | -2.134 | Highly Destabilizing | 0.901 | D | 0.825 | deleterious | D | 0.560077451 | None | None | I |
| I/T | 0.9486 | likely_pathogenic | 0.8747 | pathogenic | -1.974 | Destabilizing | 0.722 | D | 0.812 | deleterious | D | 0.53061689 | None | None | I |
| I/V | 0.1467 | likely_benign | 0.1142 | benign | -1.501 | Destabilizing | 0.008 | N | 0.279 | neutral | N | 0.479157983 | None | None | I |
| I/W | 0.9957 | likely_pathogenic | 0.9882 | pathogenic | -1.829 | Destabilizing | 0.996 | D | 0.827 | deleterious | None | None | None | None | I |
| I/Y | 0.9742 | likely_pathogenic | 0.9355 | pathogenic | -1.604 | Destabilizing | 0.961 | D | 0.799 | 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.