Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30197 | 90814;90815;90816 | chr2:178552311;178552310;178552309 | chr2:179417038;179417037;179417036 |
| N2AB | 28556 | 85891;85892;85893 | chr2:178552311;178552310;178552309 | chr2:179417038;179417037;179417036 |
| N2A | 27629 | 83110;83111;83112 | chr2:178552311;178552310;178552309 | chr2:179417038;179417037;179417036 |
| N2B | 21132 | 63619;63620;63621 | chr2:178552311;178552310;178552309 | chr2:179417038;179417037;179417036 |
| Novex-1 | 21257 | 63994;63995;63996 | chr2:178552311;178552310;178552309 | chr2:179417038;179417037;179417036 |
| Novex-2 | 21324 | 64195;64196;64197 | chr2:178552311;178552310;178552309 | chr2:179417038;179417037;179417036 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs531923761  |
-0.518 | 0.993 | N | 0.65 | 0.432 | 0.32082282376 | gnomAD-2.1.1 | 3.24E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.33707E-04 | None | 0 | 0 | 1.67504E-04 |
| E/G | rs531923761 |
-0.518 | 0.993 | N | 0.65 | 0.432 | 0.32082282376 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| E/G | rs531923761 |
-0.518 | 0.993 | N | 0.65 | 0.432 | 0.32082282376 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| E/G | rs531923761 |
-0.518 | 0.993 | N | 0.65 | 0.432 | 0.32082282376 | gnomAD-4.0.0 | 1.02693E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 9.44644E-05 | 2.84722E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.1448 | likely_benign | 0.1526 | benign | -0.316 | Destabilizing | 0.977 | D | 0.625 | neutral | N | 0.510717749 | None | None | N |
| E/C | 0.7779 | likely_pathogenic | 0.7998 | pathogenic | -0.183 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| E/D | 0.1035 | likely_benign | 0.1111 | benign | -0.217 | Destabilizing | 0.977 | D | 0.485 | neutral | N | 0.491438555 | None | None | N |
| E/F | 0.7335 | likely_pathogenic | 0.7507 | pathogenic | -0.2 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| E/G | 0.1878 | likely_benign | 0.2005 | benign | -0.495 | Destabilizing | 0.993 | D | 0.65 | neutral | N | 0.512680619 | None | None | N |
| E/H | 0.5173 | ambiguous | 0.5371 | ambiguous | 0.221 | Stabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/I | 0.2571 | likely_benign | 0.2783 | benign | 0.119 | Stabilizing | 0.998 | D | 0.761 | deleterious | None | None | None | None | N |
| E/K | 0.2841 | likely_benign | 0.2767 | benign | 0.21 | Stabilizing | 0.955 | D | 0.563 | neutral | N | 0.497057806 | None | None | N |
| E/L | 0.4144 | ambiguous | 0.4462 | ambiguous | 0.119 | Stabilizing | 0.995 | D | 0.735 | prob.delet. | None | None | None | None | N |
| E/M | 0.4652 | ambiguous | 0.4831 | ambiguous | 0.062 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| E/N | 0.2641 | likely_benign | 0.2801 | benign | -0.013 | Destabilizing | 0.995 | D | 0.719 | prob.delet. | None | None | None | None | N |
| E/P | 0.5165 | ambiguous | 0.5466 | ambiguous | -0.007 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | None | None | None | None | N |
| E/Q | 0.1904 | likely_benign | 0.1995 | benign | 0.021 | Stabilizing | 0.568 | D | 0.323 | neutral | N | 0.501714264 | None | None | N |
| E/R | 0.4225 | ambiguous | 0.4099 | ambiguous | 0.512 | Stabilizing | 0.99 | D | 0.723 | prob.delet. | None | None | None | None | N |
| E/S | 0.2027 | likely_benign | 0.2074 | benign | -0.219 | Destabilizing | 0.983 | D | 0.627 | neutral | None | None | None | None | N |
| E/T | 0.2115 | likely_benign | 0.2265 | benign | -0.073 | Destabilizing | 0.995 | D | 0.703 | prob.neutral | None | None | None | None | N |
| E/V | 0.1755 | likely_benign | 0.1944 | benign | -0.007 | Destabilizing | 0.997 | D | 0.723 | prob.delet. | N | 0.512008615 | None | None | N |
| E/W | 0.8757 | likely_pathogenic | 0.8809 | pathogenic | -0.069 | Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | N |
| E/Y | 0.6022 | likely_pathogenic | 0.6234 | pathogenic | 0.035 | Stabilizing | 0.999 | D | 0.743 | 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.