Disease: HMERF
| Position | Domain | Domain position | SNV | RS | Source | Comments | MAF | Zygosity | Structural Position | AlphaMissense (IC) | REVEL | Rhapsody | DUET | PolyPhen-2 | Condel | Q(SASA) |
Site annotation |
mCSM PPI |
Predicted PPI site |
AFR | AMR | EAS | EUR | FIN | NFE | SAS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
31709  |
Fn3-119 |
2 | P/H | rs869320739  |
Palmio (2019)
| Genetic analysis of genes in 12 HMERF families; co-segregates with condition (n = 1, 1 affected (total 2)) | None | het | 2 |
0.9968 | 0.603 | 0.744 | None | 0.999 | None | 0.1489 | None | None | N | None | None | None | None | None | None | None | 31709 |
Fn3-119 |
2 | P/R | rs869320739 |
Palmio (2013)
Hedberg (2014)
| WES/WGS prioritisation in 12 HMERF families; dominant effect, full penetrance (n = 3, 3 affected (total 6)) | None | het | 2 |
0.9921 | 0.811 | 0.464 | -0.93 | 0.235 | None | 0.1489 | None | None | N | None | None | None | None | None | None | None | 31712 |
Fn3-119 |
5 | C/R | rs869320740 |
gnomAD-2.1.1 | None | 0.00000411 | None | 5 |
0.8445 | 0.791 | 0.743 | -1.28 | 0.996 | None | 0.1205 | None | None | N | 0 | 0 | 0 | None | 0 | 0 | 9.1E-06 | 31712 |
Fn3-119 |
5 | C/R | rs869320740 |
Pfeffer (2012)
Ohlsson (2012)
Toro (2013)
Palmio (2013)
Pfeffer (2014)
Hedberg (2014)
Uruha (2015)
Yue (2015)
Palmio (2019)
Morais (2020)
Huang (2021)
| Found in multiple studies with full penetrance; WES prioritisation in single family; co-segregates in 3 families tested; WES/WGS prioritisation in 12 HMERF families, full penetrance; Genetic analysis of genes in 127 undiagnosed patients, likely MFM; Genetic analysis of genes in 12 HMERF families; WES prioritisation of single US family + 45 unrelated probands; Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF; Genetic analysis of CN patient (familial) | None | het | 5 |
0.8445 | 0.791 | 0.743 | -1.28 | 0.996 | None | 0.1205 | None | None | N | None | None | None | None | None | None | None | 31712 |
Fn3-119 |
5 | C/R | rs869320740 |
gnomAD-4.0.0 | None | 0.00000343489 | None | 5 |
0.8445 | 0.791 | 0.743 | -1.28 | 0.996 | None | 0.1205 | None | None | N | 0 | 0 | 0 | None | 1.88501E-05 | 2.7073E-06 | 0 | 31712 |
Fn3-119 |
5 | C/Y | None |
Uruha (2015)
| Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | het | 5 |
0.7862 | 0.723 | 0.674 | -1.682 | 0.996 | None | 0.1205 | None | None | N | None | None | None | None | None | None | None | 31712 |
Fn3-119 |
5 | C/W | None |
Yeo (2021)
| Genetic analysis of single KR family with HMERF; co-segregates with condition (n = 2, 2 affected (total 2), 2 predeceased with similar pathology) | None | het | 5 |
0.8964 | 0.399 | 0.679 | None | 0.999 | None | 0.1205 | None | None | N | None | None | None | None | None | None | None | 31729 |
Fn3-119 |
22 | W/C | rs869320742 |
Palmio (2013)
Hedberg (2014)
Bugiardini (2018)
Palmio (2019)
| WES/WGS prioritisation in 12 HMERF families; dominant effect, full penetrance (n = 2, 2 affected (total 4)); Genetic analysis of genes in 12 HMERF families (n = 4, 4 affected) | None | het | 24 |
0.9937 | 0.956 | 0.865 | -1.772 | 1.0 | None | 0.1098 | None | None | N | None | None | None | None | None | None | None | 31729 |
Fn3-119 |
22 | W/C | rs869320742 |
gnomAD-4.0.0 | None | 0.0000061583 | None | 24 |
0.9937 | 0.956 | 0.865 | -1.772 | 1.0 | None | 0.1098 | None | None | N | 0 | 0 | 0 | None | 0 | 8.09561E-06 | 0 | 31729 |
Fn3-119 |
22 | W/L | rs786205367 |
Izumi (2013)
| Genetic analysis of single JP family; co-segregates within family (n = 5, 5 affected (total 10)); linkage analysis; not found in ethnic controls | None | het | 24 |
0.9589 | 0.903 | 0.851 | -2.41 | 1.0 | None | 0.1098 | None | None | N | None | None | None | None | None | None | None | 31729 |
Fn3-119 |
22 | W/R | rs869320741 |
Palmio (2013)
Hedberg (2014)
Huang (2021)
| WES/WGS prioritisation in 12 HMERF families; dominant effect, unknown penetrance | None | het | 24 |
0.999 | 0.934 | 0.917 | -2.066 | 1.0 | None | 0.1098 | None | None | N | None | None | None | None | None | None | None | 31732 |
Fn3-119 |
25 | P/L | rs753334568 |
gnomAD-2.1.1 | None | 0.0000121 | None | 27 |
0.9061 | 0.727 | 0.888 | -0.671 | 1.0 | None | 0.1539 | None | None | N | 0 | 0 | 0 | None | 3.27E-05 | 0 | 1.78E-05 | 31732 |
Fn3-119 |
25 | P/L | rs753334568 |
gnomAD-3.1.2 | None | 0.0000131 | None | 27 |
0.9061 | 0.727 | 0.888 | -0.671 | 1.0 | None | 0.1539 | None | None | N | 0 | 0 | 0 | None | 0 | 2.94E-05 | 0 | 31732 |
Fn3-119 |
25 | P/L | rs753334568 |
Vasli (2012)
Pfeffer (2013)
Palmio (2013)
Hedberg (2014)
Yue (2015)
Rees (2021)
Sano (2022)
| Incomplete penetrance, more severe when homozygous; Found in genetic analysis of TTN in 30 CM patients (homozygous); genetic analysis of genes in 127 undiagnosed patients (likely MFM); WES/WGS prioritisation in 12 HMERF families; genetic analysis in single NMD patient (heterozygous); genetic analysis of CN patient (sporadic) and unaffected carrier (brother); Domain unfolded in vitro (Tm 17 degrees lower than WT) | None | hom / comp het with R34091W | 27 |
0.9061 | 0.727 | 0.888 | -0.671 | 1.0 | None | 0.1539 | None | None | N | None | None | None | None | None | None | None | 31732 |
Fn3-119 |
25 | P/L | rs753334568 |
gnomAD-4.0.0 | None | 0.00000929582 | None | 27 |
0.9061 | 0.727 | 0.888 | -0.671 | 1.0 | None | 0.1539 | None | None | N | 0 | 1.66706E-05 | 0 | None | 0 | 1.01715E-05 | 1.09786E-05 | 31784 |
Fn3-119 |
77 | A/V | rs1553520967 |
Palmio (2019)
| Genetic analysis of genes in 12 HMERF families; co-segregates with condition (n = 6, 6 affected (8 total)) | None | het | 110 |
0.874 | 0.69 | 0.68 | None | 0.946 | None | 0.0926 | None | None | N | None | None | None | None | None | None | None | 31786 |
Fn3-119 |
79 | N/K | rs869320743 |
Pfeffer (2013)
Palmio (2019)
| Genetic analysis of genes in 127 undiagnosed patients, likely MFM; co-segregates with condition (n = 2, 2 affected (total 7)) | None | het | 112 |
0.9985 | 0.842 | 0.737 | -0.663 | 1.0 | None | 0.1164 | None | None | N | None | None | None | None | None | None | None | 31786 |
Fn3-119 |
79 | N/K | rs869320743 |
gnomAD-4.0.0 | None | 0.00000120033 | None | 112 |
0.9985 | 0.842 | 0.737 | -0.663 | 1.0 | None | 0.1164 | None | None | N | 0 | 0 | 0 | None | 0 | 1.3125E-06 | 0 | 31791 |
Fn3-119 |
84 | G/D | rs869320744 |
Toro (2013)
Uruha (2015)
| WES prioritisation of single US family + 45 unrelated probands; Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | het | 118 |
0.984 | 0.944 | 0.875 | -1.821 | 1.0 | None | 0.147 | None | None | N | None | None | None | None | None | None | None | 31791 |
Fn3-119 |
84 | G/R | rs1696856005 |
Uruha (2015)
| Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | het | 118 |
0.9924 | 0.954 | 0.916 | -1.008 | 1.0 | None | 0.147 | None | None | N | None | None | None | None | None | None | None | 31791 |
Fn3-119 |
84 | G/V | None |
Uruha (2015)
| Genetic analysis of Fn3-119 in 187 MFM patients to assess diagnostic value of sub-sarcolemmal necklace alignments of cytoplasmic bodies for HMERF | None | het | 118 |
0.9787 | 0.916 | 0.903 | -0.713 | 1.0 | None | 0.147 | None | None | N | None | None | None | None | None | None | None | 34091 |
Kinase-1 |
279 | R/W | rs140319117 |
gnomAD-2.1.1 | None | 0.001015516 | None | None |
0.6435 | 0.328 | None | -0.302 | None | None | 0.3625 | None | None | N | 3.30852E-04 | 1.35793E-03 | 0 | None | 6.54E-05 | 4.19E-05 | 1.43289E-03 | 34091 |
Kinase-1 |
279 | R/W | rs140319117 |
gnomAD-3.1.2 | None | 0.00097976 | None | None |
0.6435 | 0.328 | None | -0.302 | None | None | 0.3625 | None | None | N | 2.41476E-04 | 1.2459E-03 | 0 | None | 9.44E-05 | 1.52896E-03 | 4.1425E-04 | 34091 |
Kinase-1 |
279 | R/W | rs140319117 |
1000 genomes | None | 0.000798722 | None | None |
0.6435 | 0.328 | None | -0.302 | None | None | 0.3625 | None | None | N | 0 | 1.4E-03 | 0 | 3E-03 | None | None | 0 | 34091 |
Kinase-1 |
279 | R/W | rs140319117 |
Lange (2005)
Lange (2014)
| WGS prioritisation in 2 Swedish families; greatly reduces interaction of kinase with nbr1; nbr1 and MuRF1 show diffuse localisation; comp het with Fn3-119 variants, re-classified as benign; subsequent argument it may be modulatory to incompletely penetrant P31732L variant | None | comp het with P31732L | None |
0.6435 | 0.328 | None | -0.302 | None | None | 0.3625 | None | None | N | None | None | None | None | None | None | None | 34091 |
Kinase-1 |
279 | R/W | rs140319117 |
gnomAD-4.0.0 | None | 0.001376247 | None | None |
0.6435 | 0.328 | None | -0.302 | None | None | 0.3625 | None | None | N | 2.66667E-04 | 1.35018E-03 | 2.22856E-05 | None | 4.7957E-05 | 1.62993E-03 | 1.31749E-04 |