Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2324 | 7195;7196;7197 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
| N2AB | 2324 | 7195;7196;7197 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
| N2A | 2324 | 7195;7196;7197 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
| N2B | 2278 | 7057;7058;7059 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
| Novex-1 | 2278 | 7057;7058;7059 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
| Novex-2 | 2278 | 7057;7058;7059 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
| Novex-3 | 2324 | 7195;7196;7197 | chr2:178774294;178774293;178774292 | chr2:179639021;179639020;179639019 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/M | rs760633130  |
-0.223 | 0.996 | D | 0.679 | 0.52 | None | gnomAD-2.1.1 | 7.08E-05 | None | None | None | None | N | None | 8.01E-05 | 0 | None | 0 | 2.00702E-04 | None | 3.26627E-04 | None | 3.98E-05 | 2.33E-05 | 0 |
| T/M | rs760633130 |
-0.223 | 0.996 | D | 0.679 | 0.52 | None | gnomAD-3.1.2 | 5.92E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 9.60799E-04 | None | 0 | 3.18471E-03 | 1.47E-05 | 2.07641E-04 | 0 |
| T/M | rs760633130 |
-0.223 | 0.996 | D | 0.679 | 0.52 | None | gnomAD-4.0.0 | 4.08917E-05 | None | None | None | None | N | None | 5.33333E-05 | 0 | None | 0 | 2.45098E-04 | None | 1.56221E-05 | 1.65017E-04 | 1.10172E-05 | 3.953E-04 | 0 |
| T/P | None | None | 0.988 | D | 0.671 | 0.595 | 0.534668972696 | gnomAD-4.0.0 | 1.59057E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02133E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1017 | likely_benign | 0.1006 | benign | -1.032 | Destabilizing | 0.704 | D | 0.546 | neutral | N | 0.511264372 | None | None | N |
| T/C | 0.4174 | ambiguous | 0.449 | ambiguous | -0.874 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| T/D | 0.6386 | likely_pathogenic | 0.6394 | pathogenic | -0.943 | Destabilizing | 0.939 | D | 0.669 | neutral | None | None | None | None | N |
| T/E | 0.4807 | ambiguous | 0.4748 | ambiguous | -0.884 | Destabilizing | 0.939 | D | 0.666 | neutral | None | None | None | None | N |
| T/F | 0.2248 | likely_benign | 0.2157 | benign | -0.982 | Destabilizing | 0.982 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/G | 0.419 | ambiguous | 0.4265 | ambiguous | -1.335 | Destabilizing | 0.939 | D | 0.669 | neutral | None | None | None | None | N |
| T/H | 0.2644 | likely_benign | 0.2661 | benign | -1.574 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| T/I | 0.1154 | likely_benign | 0.1097 | benign | -0.293 | Destabilizing | 0.884 | D | 0.665 | neutral | None | None | None | None | N |
| T/K | 0.2955 | likely_benign | 0.2947 | benign | -0.828 | Destabilizing | 0.967 | D | 0.663 | neutral | D | 0.570962595 | None | None | N |
| T/L | 0.0936 | likely_benign | 0.0893 | benign | -0.293 | Destabilizing | 0.046 | N | 0.399 | neutral | None | None | None | None | N |
| T/M | 0.076 | likely_benign | 0.0845 | benign | -0.041 | Destabilizing | 0.996 | D | 0.679 | prob.neutral | D | 0.572421736 | None | None | N |
| T/N | 0.1673 | likely_benign | 0.1661 | benign | -1.018 | Destabilizing | 0.939 | D | 0.64 | neutral | None | None | None | None | N |
| T/P | 0.8209 | likely_pathogenic | 0.832 | pathogenic | -0.507 | Destabilizing | 0.988 | D | 0.671 | neutral | D | 0.639318352 | None | None | N |
| T/Q | 0.2819 | likely_benign | 0.2751 | benign | -1.158 | Destabilizing | 0.991 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/R | 0.2323 | likely_benign | 0.2383 | benign | -0.651 | Destabilizing | 0.995 | D | 0.671 | neutral | D | 0.535698187 | None | None | N |
| T/S | 0.1369 | likely_benign | 0.1381 | benign | -1.276 | Destabilizing | 0.159 | N | 0.229 | neutral | D | 0.541083353 | None | None | N |
| T/V | 0.1113 | likely_benign | 0.1084 | benign | -0.507 | Destabilizing | 0.884 | D | 0.62 | neutral | None | None | None | None | N |
| T/W | 0.5991 | likely_pathogenic | 0.6005 | pathogenic | -0.923 | Destabilizing | 0.999 | D | 0.702 | prob.neutral | None | None | None | None | N |
| T/Y | 0.2981 | likely_benign | 0.2937 | benign | -0.654 | Destabilizing | 0.997 | D | 0.675 | neutral | 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.