Disease: TMD
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 | 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 |