Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23895 | 71908;71909;71910 | chr2:178574449;178574448;178574447 | chr2:179439176;179439175;179439174 |
| N2AB | 22254 | 66985;66986;66987 | chr2:178574449;178574448;178574447 | chr2:179439176;179439175;179439174 |
| N2A | 21327 | 64204;64205;64206 | chr2:178574449;178574448;178574447 | chr2:179439176;179439175;179439174 |
| N2B | 14830 | 44713;44714;44715 | chr2:178574449;178574448;178574447 | chr2:179439176;179439175;179439174 |
| Novex-1 | 14955 | 45088;45089;45090 | chr2:178574449;178574448;178574447 | chr2:179439176;179439175;179439174 |
| Novex-2 | 15022 | 45289;45290;45291 | chr2:178574449;178574448;178574447 | chr2:179439176;179439175;179439174 |
| 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/N | rs1208236175  |
-1.068 | 0.859 | N | 0.588 | 0.475 | 0.797541934475 | 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 |
| I/N | rs1208236175 |
-1.068 | 0.859 | N | 0.588 | 0.475 | 0.797541934475 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs1208236175 |
-1.068 | 0.859 | N | 0.588 | 0.475 | 0.797541934475 | gnomAD-4.0.0 | 1.23954E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.6954E-06 | 0 | 0 |
| I/T | None | None | 0.124 | N | 0.42 | 0.3 | 0.452737964553 | gnomAD-4.0.0 | 2.05283E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69865E-06 | 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 | 0.3418 | ambiguous | 0.3921 | ambiguous | -1.693 | Destabilizing | 0.157 | N | 0.393 | neutral | None | None | None | None | N |
| I/C | 0.6828 | likely_pathogenic | 0.714 | pathogenic | -0.784 | Destabilizing | 0.909 | D | 0.447 | neutral | None | None | None | None | N |
| I/D | 0.8055 | likely_pathogenic | 0.8243 | pathogenic | -1.091 | Destabilizing | 0.726 | D | 0.577 | neutral | None | None | None | None | N |
| I/E | 0.6961 | likely_pathogenic | 0.7243 | pathogenic | -1.027 | Destabilizing | 0.726 | D | 0.587 | neutral | None | None | None | None | N |
| I/F | 0.2107 | likely_benign | 0.2138 | benign | -1.103 | Destabilizing | 0.497 | N | 0.449 | neutral | D | 0.523193975 | None | None | N |
| I/G | 0.7088 | likely_pathogenic | 0.7551 | pathogenic | -2.068 | Highly Destabilizing | 0.726 | D | 0.581 | neutral | None | None | None | None | N |
| I/H | 0.6037 | likely_pathogenic | 0.6277 | pathogenic | -1.262 | Destabilizing | 0.968 | D | 0.607 | neutral | None | None | None | None | N |
| I/K | 0.5785 | likely_pathogenic | 0.5683 | pathogenic | -0.998 | Destabilizing | 0.726 | D | 0.588 | neutral | None | None | None | None | N |
| I/L | 0.1024 | likely_benign | 0.1095 | benign | -0.706 | Destabilizing | None | N | 0.101 | neutral | N | 0.400384982 | None | None | N |
| I/M | 0.1035 | likely_benign | 0.1065 | benign | -0.463 | Destabilizing | 0.497 | N | 0.455 | neutral | N | 0.468820773 | None | None | N |
| I/N | 0.3389 | likely_benign | 0.3727 | ambiguous | -0.951 | Destabilizing | 0.859 | D | 0.588 | neutral | N | 0.449234934 | None | None | N |
| I/P | 0.9349 | likely_pathogenic | 0.937 | pathogenic | -1.006 | Destabilizing | 0.89 | D | 0.584 | neutral | None | None | None | None | N |
| I/Q | 0.5436 | ambiguous | 0.5757 | pathogenic | -1.045 | Destabilizing | 0.89 | D | 0.589 | neutral | None | None | None | None | N |
| I/R | 0.4776 | ambiguous | 0.4661 | ambiguous | -0.491 | Destabilizing | 0.726 | D | 0.585 | neutral | None | None | None | None | N |
| I/S | 0.3581 | ambiguous | 0.3989 | ambiguous | -1.611 | Destabilizing | 0.497 | N | 0.471 | neutral | N | 0.448752145 | None | None | N |
| I/T | 0.2129 | likely_benign | 0.2474 | benign | -1.426 | Destabilizing | 0.124 | N | 0.42 | neutral | N | 0.415383359 | None | None | N |
| I/V | 0.0887 | likely_benign | 0.0985 | benign | -1.006 | Destabilizing | 0.001 | N | 0.139 | neutral | N | 0.415141003 | None | None | N |
| I/W | 0.8252 | likely_pathogenic | 0.819 | pathogenic | -1.272 | Destabilizing | 0.968 | D | 0.63 | neutral | None | None | None | None | N |
| I/Y | 0.5412 | ambiguous | 0.5497 | ambiguous | -0.988 | Destabilizing | 0.726 | D | 0.424 | 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.