Disease: MD
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
238  |
None | None | E/Q | None |
Peddareddygari (2022) 
| Segregation analysis in single LGMD family, co-segregates with condition in affected mother and son, absent in unaffected son, co-inherited with Q466R | None | comp het with Q466R (in cis) | None |
0.4499 | 0.218 | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | 466 |
None | None | Q/R | rs150282120 |
gnomAD-2.1.1 | None | 0.0000239 | None | None |
0.1025 | 0.199 | None | None | None | None | None | None | None | None | 3.69094E-04 | 0 | 0 | None | 0 | 0 | 0 | 466 |
None | None | Q/R | rs150282120 |
gnomAD-3.1.2 | None | 0.0000328 | None | None |
0.1025 | 0.199 | None | None | None | None | None | None | None | None | 1.20587E-04 | 0 | 0 | None | 0 | 0 | 0 | 466 |
None | None | Q/R | rs150282120 |
Peddareddygari (2022)
| Segregation analysis in single LGMD family, co-segregates with condition in affected mother and son, absent in unaffected son, co-inherited with E238Q | None | comp het with E238Q (in cis) | None |
0.1025 | 0.199 | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | 466 |
None | None | Q/R | rs150282120 |
gnomAD-4.0.0 | None | 0.00000619554 | None | None |
0.1025 | 0.199 | None | None | None | None | None | None | None | None | 1.33437E-04 | 0 | 0 | None | 0 | 0 | 0 | 1034 |
None | None | V/M | rs142951505 |
gnomAD-2.1.1 | None | 0.000816159 | None | None |
0.2081 | 0.302 | None | None | None | None | None | None | None | None | 0 | 2.5418E-04 | 0 | None | 6.8614E-04 | 1.91235E-03 | 1.12232E-03 | 1034 |
None | None | V/M | rs142951505 |
gnomAD-3.1.2 | None | 0.000611126 | None | None |
0.2081 | 0.302 | None | None | None | None | None | None | None | None | 1.93069E-04 | 1.3089E-04 | 0 | None | 1.31827E-03 | 9.55377E-04 | 6.21118E-04 | 1034 |
None | None | V/M | rs142951505 |
1000 genomes | None | 0.000399361 | None | None |
0.2081 | 0.302 | None | None | None | None | None | None | None | None | 0 | 0 | 0 | 1E-03 | None | None | 1E-03 | 1034 |
None | None | V/M | rs142951505 |
Vasli (2012)
| Genetic analysis of MD patients; unknown inheritance (n = 2, 2 affected (total 3)); variant prioritisation; comp het with A18983T | None | comp het with A18983T | None |
0.2081 | 0.302 | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | 1034 |
None | None | V/M | rs142951505 |
gnomAD-4.0.0 | None | 0.000955558 | None | None |
0.2081 | 0.302 | None | None | None | None | None | None | None | None | 1.33358E-04 | 2.33287E-04 | 0 | None | 2.56194E-03 | 1.06711E-03 | 6.92201E-04 | 18983 |
Fn3-25 |
100 | A/T | rs377000174 |
gnomAD-2.1.1 | None | 0.0000932 | None | 130 |
0.7957 | 0.212 | 0.632 | -1.953 | 0.919 | None | 0.0794 | None | None | N | 0 | 5.68E-05 | 0 | None | 0 | 0 | 1.80616E-04 | 18983 |
Fn3-25 |
100 | A/T | rs377000174 |
gnomAD-3.1.2 | None | 0.0000657 | None | 130 |
0.7957 | 0.212 | 0.632 | -1.953 | 0.919 | None | 0.0794 | None | None | N | 0 | 0 | 0 | None | 0 | 1.17644E-04 | 0 | 18983 |
Fn3-25 |
100 | A/T | rs377000174 |
Vasli (2012)
| Genetic analysis of MD patients; unknown inheritance (n = 2, 2 affected (total 3)); variant prioritisation; comp het with V1034M | None | comp het with V1034M | 130 |
0.7957 | 0.212 | 0.632 | -1.953 | 0.919 | None | 0.0794 | None | None | N | None | None | None | None | None | None | None | 18983 |
Fn3-25 |
100 | A/T | rs377000174 |
gnomAD-4.0.0 | None | 0.00010293 | None | 130 |
0.7957 | 0.212 | 0.632 | -1.953 | 0.919 | None | 0.0794 | None | None | N | 1.33622E-05 | 3.34292E-05 | 0 | None | 0 | 1.33968E-04 | 0 | 30723 |
Fn3-112 |
5 | P/S | rs758537709 |
gnomAD-2.1.1 | None | 0.0000618 | None | 5 |
0.956 | 0.861 | 0.845 | -2.849 | 1.0 | None | 0.1353 | None | None | N | 0 | 0 | 0 | None | 0 | 1.21971E-04 | 1.03339E-04 | 30723 |
Fn3-112 |
5 | P/S | rs758537709 |
gnomAD-3.1.2 | None | 0.000092 | None | 5 |
0.956 | 0.861 | 0.845 | -2.849 | 1.0 | None | 0.1353 | None | None | N | 0 | 0 | 0 | None | 1.88537E-04 | 1.76414E-04 | 0 | 30723 |
Fn3-112 |
5 | P/S | rs758537709 |
Evila (2014)
Lopez-Bravo (2021)
| Genetic analysis of genes in patients with previously reported TTN variants; found in single patient comp het with TMD-associated indel FINmaj (EVTW35927delinsVKEK); more severe TMD than others in phenotype; subsequent identification in single patient with distal myopathy of lower limbs and DCM; homozygous in affected patient, heterozygous in both unaffected parents | None | comp het with 35927delinsEVTW>VKEK (FINmaj) / hom | 5 |
0.956 | 0.861 | 0.845 | -2.849 | 1.0 | None | 0.1353 | None | None | N | None | None | None | None | None | None | None | 30723 |
Fn3-112 |
5 | P/S | rs758537709 |
gnomAD-4.0.0 | None | 0.0000953693 | None | 5 |
0.956 | 0.861 | 0.845 | -2.849 | 1.0 | None | 0.1353 | None | None | N | 0 | 0 | 0 | None | 1.72788E-04 | 1.18445E-04 | 0 | 31429 |
Fn3-117 |
22 | W/R | None |
Evila (2016)
| Genetic analysis of genes in 10 TMD families; co-segregation in 2-generation family (recessive inheritance, n = 3, 1 affected (total 5; disease state only where compound heterozygous for both W31429R and R21209*)); variant prioritisation; comp het with R21209* | None | comp het with R21209* | 24 |
0.9997 | 0.861 | 0.913 | -1.936 | 1.0 | None | 0.1197 | None | None | N | None | None | None | None | None | None | None | 31429 |
Fn3-117 |
22 | W/R | None | gnomAD-4.0.0 | None | 0.00000120032 | None | 24 |
0.9997 | 0.861 | 0.913 | -1.936 | 1.0 | None | 0.1197 | None | None | N | 0 | 1.01626E-03 | 0 | None | 0 | 0 | 0 | 35915 |
Ig-169 |
19 | T/P | None |
Evila (2016)
| Genetic analysis of genes in 10 TMD families; co-segregation in 2-generation family (recessive inheritance, n = 3, 3 affected (total 4)); variant prioritisation; comp het with E28338fs | None | comp het with E28338fs | 29 |
0.794 | 0.467 | 0.751 | -0.588 | 0.999 | None | 0.1191 | None | -1.476(OBSL1) -0.66(OBSCN) | N | None | None | None | None | None | None | None | 35915 |
Ig-169 |
19 | T/P | None | gnomAD-4.0.0 | None | 0.00000120032 | None | 29 |
0.794 | 0.467 | 0.751 | -0.588 | 0.999 | None | 0.1191 | None | -1.476(OBSL1) -0.66(OBSCN) | N | 6.33473E-05 | 0 | 0 | None | 0 | 0 | 0 | 35930 |
Ig-169 |
34 | W/R | rs1018591024 |
Zheng (2016)
| WES prioritisation of single 5-generation CN family; co-segregation within family (recessive inheritance, n = 3, 3 affected, (6 total)) | None | hom | 48 |
0.9987 | 0.938 | 0.836 | -2.172 | 1.0 | None | 0.1526 | None | -0.843(OBSL1) -1.308(OBSCN) | N | None | None | None | None | None | None | None | 35930 |
Ig-169 |
34 | W/R | rs1018591024 |
gnomAD-4.0.0 | None | 0.0000027366 | None | 48 |
0.9987 | 0.938 | 0.836 | -2.172 | 1.0 | None | 0.1526 | None | -0.843(OBSL1) -1.308(OBSCN) | N | 0 | 0 | 0 | None | 0 | 3.59762E-06 | 0 | 35946 |
Ig-169 |
50 | H/P | rs281864931 |
Pollazzon (2010)
Rudloff (2015)
| Genetic analysis of TTN in single 3-generation ITA family; co-segregates with disease (n = 5, 5 affected (total 7)); Domain unfolds at body temperature; eliminates binding to OBSCN-Ig1; low expression; monomeric | None | het | 122 |
0.7767 | 0.628 | 0.721 | -0.76 | 0.998 | None | 0.2633 | None | -1.036(OBSL1) -0.709(OBSCN) | N | None | None | None | None | None | None | None | 35947 |
Ig-169 |
51 | I/N | None | gnomAD-2.1.1 | None | 0.00000401 | None | 123 |
0.7303 | 0.652 | 0.701 | -1.845 | 0.901 | None | 0.1542 | None | -0.949(OBSL1) -0.17(OBSCN) | N | 0 | 0 | 0 | None | 0 | 0 | 8.85E-06 | 35947 |
Ig-169 |
51 | I/N | None | gnomAD-3.1.2 | None | 0.0000131 | None | 123 |
0.7303 | 0.652 | 0.701 | -1.845 | 0.901 | None | 0.1542 | None | -0.949(OBSL1) -0.17(OBSCN) | N | 0 | 0 | 0 | None | 0 | 2.94E-05 | 0 | 35947 |
Ig-169 |
51 | I/N | None |
Van den Bergh (2003)
Rudloff (2015)
Evila (2016)
| Genetic analysis of TTN in 3-generation BEL family with TMD, incomplete penetrance (n = 6, 5 affected, 1 unaffected carrier (total 9)); Genetic analysis of genes in 10 TMD families; co-segregation in 2-generation family (recessive inheritance, n = 2, 1 affected (total 3; disease state only where compound heterozygous for both I35947N and Q22507*));variant prioritisation; comp het with Q22507*; No significant difference in domain stability; does not affect binding to OBSCN-Ig1; normal expression; monomeric | None | het / comp het with Q22507* | 123 |
0.7303 | 0.652 | 0.701 | -1.845 | 0.901 | None | 0.1542 | None | -0.949(OBSL1) -0.17(OBSCN) | N | None | None | None | None | None | None | None | 35947 |
Ig-169 |
51 | I/N | None | gnomAD-4.0.0 | None | 0.0000111535 | None | 123 |
0.7303 | 0.652 | 0.701 | -1.845 | 0.901 | None | 0.1542 | None | -0.949(OBSL1) -0.17(OBSCN) | N | 0 | 0 | 0 | None | 0 | 1.52557E-05 | 0 | 35956 |
Ig-169 |
60 | L/P | rs267607156 |
Hackman (2002)
Rudloff (2015)
| Genetic analysis of single FRA family; co-segregates within family (n = 3, 3 affected (7 total)); Severe misfolding of domain; eliminates binding to OBSCN-Ig1; low expression; monomeric | None | het | 138 |
0.999 | 0.788 | 0.895 | -1.745 | 1.0 | None | 0.1078 | None | -0.747(OBSL1) -0.71(OBSCN) | N | None | None | None | None | None | None | None |