Disease: DCM
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
54  |
Ig-1 |
49 | V/M | rs139517732  |
gnomAD-2.1.1 | None | 0.0000425 | None | 121 |
0.2615 | 0.39 | 0.517 | -0.932 | 0.662 | None | 0.1304 | None | -1.137(TCAP) | N | 0 | 2.82E-05 | 5.52597E-04 | None | 0 | 0 | 0 | 54 |
Ig-1 |
49 | V/M | rs139517732 |
gnomAD-3.1.2 | None | 0.0000394 | None | 121 |
0.2615 | 0.39 | 0.517 | -0.932 | 0.662 | None | 0.1304 | None | -1.137(TCAP) | N | 0 | 6.54E-05 | 9.63391E-04 | None | 0 | 0 | 0 | 54 |
Ig-1 |
49 | V/M | rs139517732 |
1000 genomes | None | 0.000599042 | None | 121 |
0.2615 | 0.39 | 0.517 | -0.932 | 0.662 | None | 0.1304 | None | -1.137(TCAP) | N | 0 | 0 | 3E-03 | 0 | None | None | 0 | 54 |
Ig-1 |
49 | V/M | rs139517732 |
Itoh-Satoh (2002)
Kumar (2016)
| Genetic analysis of JP DCM families, unknown penetrance; decreases binding of TTN to TCAP (Y2H assay); Variant prioritisation; filtering with pathogenicity/stability tools; MD analysis of binding of TTN to TCAP | None | het | 121 |
0.2615 | 0.39 | 0.517 | -0.932 | 0.662 | None | 0.1304 | None | -1.137(TCAP) | N | None | None | None | None | None | None | None | 54 |
Ig-1 |
49 | V/M | rs139517732 |
gnomAD-4.0.0 | None | 0.0000371722 | None | 121 |
0.2615 | 0.39 | 0.517 | -0.932 | 0.662 | None | 0.1304 | None | -1.137(TCAP) | N | 1.33284E-05 | 3.33178E-05 | 1.11458E-03 | None | 0 | 3.38981E-06 | 0 | 178 |
Ig-2 |
75 | A/D | None |
Hastings (2016)
Jiang (2021)
| Linkage analysis in single 3-generation DCM family, co-segregates with condition (n = 8, 8 affected (14 total)); features of LVNC; domain destabilisation and impaired TCAP binding in vitro; knock-in mice mutant show phenotype under challenge conditions | None | het | 158 |
0.9987 | 0.833 | 0.571 | -3.04 | 0.993 | None | 0.0809 | None | -1.921(TCAP) | N | None | None | None | None | None | None | None | 743 |
None | None | A/V | rs267607157 |
gnomAD-3.1.2 | None | 0.0000131 | None | None |
0.1042 | 0.273 | None | None | None | None | None | None | None | None | 0 | 0 | 3.84911E-04 | None | 0 | 0 | 0 | 743 |
None | None | A/V | rs267607157 |
Itoh-Satoh (2002)
| Genetic analysis of JP DCM families, unknown penetrance; decreases binding of TTN to ACTN1 (Y2H assay) | None | het | None |
0.1042 | 0.273 | None | None | None | None | None | None | None | None | None | None | None | None | None | None | None | 743 |
None | None | A/V | rs267607157 |
gnomAD-4.0.0 | None | 0.000015368 | None | None |
0.1042 | 0.273 | None | None | None | None | None | None | None | None | 0 | 0 | 2.90909E-04 | None | 0 | 0 | 0 | 976 |
Ig-3 |
34 | W/R | rs267607155 |
Gerull (2002)
Herman (2012)
| Linkage analysis in single DCM family, incomplete penetrance (n = 15, 11 affected, 4 unaffected carriers (total 35)) | None | het / comp het with R21201* | 48 |
0.9999 | 0.96 | 0.824 | -2.071 | 1.0 | None | 0.1431 | None | None | N | None | None | None | None | None | None | None | 4714 |
Ig-30 |
15 | G/D | rs750125429 |
gnomAD-2.1.1 | None | 0.0000823 | None | 24 |
0.8677 | 0.814 | 0.791 | -0.914 | 0.997 | None | 0.3238 | None | None | I | 0 | 0 | 1.08348E-03 | None | 0 | 0 | 1.56E-05 | 4714 |
Ig-30 |
15 | G/D | rs750125429 |
gnomAD-3.1.2 | None | 0.0000329 | None | 24 |
0.8677 | 0.814 | 0.791 | -0.914 | 0.997 | None | 0.3238 | None | None | I | 0 | 0 | 9.61908E-04 | None | 0 | 0 | 0 | 4714 |
Ig-30 |
15 | G/D | rs750125429 |
Liu (2008)
| Genetic analysis of CN DCM families (n = 2, 2 affected) | None | het | 24 |
0.8677 | 0.814 | 0.791 | -0.914 | 0.997 | None | 0.3238 | None | None | I | None | None | None | None | None | None | None | 4714 |
Ig-30 |
15 | G/D | rs750125429 |
gnomAD-4.0.0 | None | 0.0000235542 | None | 24 |
0.8677 | 0.814 | 0.791 | -0.914 | 0.997 | None | 0.3238 | None | None | I | 0 | 0 | 6.92242E-04 | None | 0 | 5.0863E-06 | 0 | 4780 |
Ig-30 |
81 | S/N | rs147879266 |
gnomAD-2.1.1 | None | 0.0000893 | None | 165 |
0.258 | 0.207 | 0.452 | 0.027 | 0.979 | None | 0.3911 | None | None | I | 0 | 0 | 1.02627E-03 | None | 1.30787E-04 | 0 | 7.82E-06 | 4780 |
Ig-30 |
81 | S/N | rs147879266 |
gnomAD-3.1.2 | None | 0.0000526 | None | 165 |
0.258 | 0.207 | 0.452 | 0.027 | 0.979 | None | 0.3911 | None | None | I | 0 | 0 | 7.70713E-04 | None | 0 | 1.47E-05 | 6.21633E-04 | 4780 |
Ig-30 |
81 | S/N | rs147879266 |
1000 genomes | None | 0.000199681 | None | 165 |
0.258 | 0.207 | 0.452 | 0.027 | 0.979 | None | 0.3911 | None | None | I | 0 | 0 | 1E-03 | 0 | None | None | 0 | 4780 |
Ig-30 |
81 | S/N | rs147879266 |
Itoh-Satoh (2002)
| Genetic analysis of JP DCM families | None | het | 165 |
0.258 | 0.207 | 0.452 | 0.027 | 0.979 | None | 0.3911 | None | None | I | None | None | None | None | None | None | None | 4780 |
Ig-30 |
81 | S/N | rs147879266 |
gnomAD-4.0.0 | None | 0.0000439978 | None | 165 |
0.258 | 0.207 | 0.452 | 0.027 | 0.979 | None | 0.3911 | None | None | I | 0 | 0 | 1.04794E-03 | None | 0 | 3.39068E-06 | 1.64712E-04 | 4854 |
Ig-31 |
60 | L/F | rs1196213888 |
gnomAD-2.1.1 | None | 0.00000402 | None | 140 |
0.1717 | 0.489 | 0.731 | -1.755 | 0.942 | None | 0.0802 | None | None | N | 0 | 2.9E-05 | 0 | None | 0 | 0 | 0 | 4854 |
Ig-31 |
60 | L/F | rs1196213888 |
gnomAD-3.1.2 | None | 0.0000263 | None | 140 |
0.1717 | 0.489 | 0.731 | -1.755 | 0.942 | None | 0.0802 | None | None | N | 2.41E-05 | 1.30959E-04 | 0 | None | 0 | 0 | 0 | 4854 |
Ig-31 |
60 | L/F | rs1196213888 |
Roncarati (2013)
| WES prioritisation in single DCM family; co-segregates with severe phenotype when inherited alongside LMNA variant K219T (n = 5, 5 severe phenotype (total 16)) | None | het; co-inherited with LMNA mutant p.K219T | 140 |
0.1717 | 0.489 | 0.731 | -1.755 | 0.942 | None | 0.0802 | None | None | N | None | None | None | None | None | None | None | 4854 |
Ig-31 |
60 | L/F | rs1196213888 |
gnomAD-4.0.0 | None | 0.00000768582 | None | 140 |
0.1717 | 0.489 | 0.731 | -1.755 | 0.942 | None | 0.0802 | None | None | N | 1.69107E-05 | 5.08423E-05 | 0 | None | 0 | 0 | 1.34005E-05 | 13702 |
Ig-87 |
19 | S/P | rs72650078 |
gnomAD-3.1.2 | None | 0.00000658 | None | 25 |
0.5141 | 0.463 | 0.647 | -0.375 | 0.999 | None | 0.1938 | None | None | N | 0 | 0 | 0 | None | 0 | 1.47E-05 | 0 | 13702 |
Ig-87 |
19 | S/P | rs72650078 |
Begay (2015)
Zuo (2021)
| WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (total 3)); moderate destabilisation of domain (SM-AFM) | None | het | 25 |
0.5141 | 0.463 | 0.647 | -0.375 | 0.999 | None | 0.1938 | None | None | N | None | None | None | None | None | None | None | 13702 |
Ig-87 |
19 | S/P | rs72650078 |
gnomAD-4.0.0 | None | 0.00000640861 | None | 25 |
0.5141 | 0.463 | 0.647 | -0.375 | 0.999 | None | 0.1938 | None | None | N | 0 | 0 | 0 | None | 0 | 1.19705E-05 | 0 | 14640 |
Ig-97 |
55 | R/C | rs72650088 |
gnomAD-2.1.1 | None | 0.0000282 | None | 136 |
0.313 | 0.296 | 0.867 | -1.68 | 1.0 | None | 0.124 | None | None | N | 0 | 0 | 0 | None | 0 | 0 | 6.23E-05 | 14640 |
Ig-97 |
55 | R/C | rs72650088 |
gnomAD-3.1.2 | None | 0.0000197 | None | 136 |
0.313 | 0.296 | 0.867 | -1.68 | 1.0 | None | 0.124 | None | None | N | 0 | 0 | 0 | None | 0 | 4.41E-05 | 0 | 14640 |
Ig-97 |
55 | R/C | rs72650088 |
Begay (2015)
Zuo (2021)
| WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (3 total)); significant destabilisation of domain (SM-AFM) | None | comp het with E29590Q | 136 |
0.313 | 0.296 | 0.867 | -1.68 | 1.0 | None | 0.124 | None | None | N | None | None | None | None | None | None | None | 14640 |
Ig-97 |
55 | R/C | rs72650088 |
gnomAD-4.0.0 | None | 0.0000216969 | None | 136 |
0.313 | 0.296 | 0.867 | -1.68 | 1.0 | None | 0.124 | None | None | N | 0 | 0 | 2.23604E-05 | None | 0 | 2.7128E-05 | 1.0981E-05 | 28118 |
Fn3-92 |
64 | R/H | rs72648220 |
gnomAD-2.1.1 | None | 0.0000363 | None | 96 |
0.0963 | 0.299 | 0.585 | -0.514 | 1.0 | None | 0.8932 | None | None | I | 0 | 8.71E-05 | 5.6E-05 | None | 0 | 0 | 4.46E-05 | 28118 |
Fn3-92 |
64 | R/H | rs72648220 |
gnomAD-3.1.2 | None | 0.0000526 | None | 96 |
0.0963 | 0.299 | 0.585 | -0.514 | 1.0 | None | 0.8932 | None | None | I | 7.24E-05 | 1.3101E-04 | 0 | None | 0 | 4.41E-05 | 0 | 28118 |
Fn3-92 |
64 | R/H | rs72648220 |
1000 genomes | None | 0.000199681 | None | 96 |
0.0963 | 0.299 | 0.585 | -0.514 | 1.0 | None | 0.8932 | None | None | I | 0 | 1.4E-03 | 0 | 0 | None | None | 0 | 28118 |
Fn3-92 |
64 | R/H | rs72648220 |
Begay (2015)
| WGS prioritisation; filtering with ANNOVAR; co-segregates within family (n = 2, 2 affected (total 2)) | None | het | 96 |
0.0963 | 0.299 | 0.585 | -0.514 | 1.0 | None | 0.8932 | None | None | I | None | None | None | None | None | None | None | 28118 |
Fn3-92 |
64 | R/H | rs72648220 |
gnomAD-4.0.0 | None | 0.0000185924 | None | 96 |
0.0963 | 0.299 | 0.585 | -0.514 | 1.0 | None | 0.8932 | None | None | I | 5.33248E-05 | 1.0001E-04 | 0 | None | 0 | 1.61057E-05 | 0 | 29303 |
Fn3-101 |
67 | S/G | rs72648231 |
gnomAD-3.1.2 | None | 0.00000657 | None | 98 |
0.1133 | 0.189 | 0.391 | -0.938 | 0.948 | None | 0.3595 | None | None | N | 0 | 0 | 0 | None | 0 | 1.47E-05 | 0 | 29303 |
Fn3-101 |
67 | S/G | rs72648231 |
Begay (2015)
| WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (total 2)); LMNA variant also observed | None | het; co-inherited with LMNA mutant c.936G>A | 98 |
0.1133 | 0.189 | 0.391 | -0.938 | 0.948 | None | 0.3595 | None | None | N | None | None | None | None | None | None | None | 29303 |
Fn3-101 |
67 | S/G | rs72648231 |
gnomAD-4.0.0 | None | 0.00000768472 | None | 98 |
0.1133 | 0.189 | 0.391 | -0.938 | 0.948 | None | 0.3595 | None | None | N | 0 | 0 | 0 | None | 0 | 1.4355E-05 | 0 | 29590 |
Fn3-103 |
58 | E/Q | rs72648236 |
gnomAD-2.1.1 | None | 0.00000402 | None | 88 |
0.1587 | 0.256 | 0.401 | -0.202 | 0.891 | None | 0.563 | None | None | N | 0 | 0 | 0 | None | 0 | 0 | 8.88E-06 | 29590 |
Fn3-103 |
58 | E/Q | rs72648236 |
Begay (2015)
| WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (total 3)) | None | comp het with R14640C | 88 |
0.1587 | 0.256 | 0.401 | -0.202 | 0.891 | None | 0.563 | None | None | N | None | None | None | None | None | None | None | 29590 |
Fn3-103 |
58 | E/Q | rs72648236 |
gnomAD-4.0.0 | None | 0.00000159104 | None | 88 |
0.1587 | 0.256 | 0.401 | -0.202 | 0.891 | None | 0.563 | None | None | N | 0 | 0 | 0 | None | 0 | 2.85778E-06 | 0 |