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. 2021 Feb 15;10(5):e018236. doi: 10.1161/JAHA.120.018236

Table 1.

Candidate Variants of FHOD3 Detected in Patients With HCM and Controls

Transcript Effect (NM_ 001281740.1) Protein (NP_001268669.1) Type Variant Classification* SNP FHOD3 Domain CADD SIFT Polyphen GnomAD MAF% ExAC MAF% In‐House MAF% Subject Identifier (Phenotype) Sarcomere Gene Variants
c.274C>T p.Arg92Trp Missense VUS rs759696197 GBD/FH3 27.1 0.005 0.967 0.0032 0.0051 0.0284 H8267 (HCM) MYH7, p.Arg453Cys
c.562C>T p.Arg188Cys Missense VUS rs143579901 GBD/FH3 24.2 0.001 0.015 0.0032 0 0.0284 H7105 (HCM) None
c.646G>A p.Val216Ile Missense VUS rs551483382 GBD/FH3 26.6 0.004 0.758 0.0084 0.0084 0.0284 H7191 (HCM) MYH7, p.Glu930Lys
c.776C>T p.Thr259Met Missense VUS rs770013602 GBD/FH3 26.2 0.008 0.414 0.0096 0.0165 0.0284 HT065 (HCM) None
c.796A>G p.Met266Val Missense VUS Novel GBD/FH3 24.1 0.187 0.21 0 0 0.0284 A073 (control) None
c.1007G>A p.Ser336Asn Missense VUS Novel GBD/FH3 13.15 NA NA 0 0 0.0284 H8138 (HCM) None
c.1063C>T p.Arg355Trp Missense VUS Novel GBD/FH3 25.9 0.001 0.471 0 0 0.0284 S285 (HCM) None
c.1097C>T p.Ser366Leu Missense VUS rs747730516 GBD/FH3 27.4 0.001 0.982 0.0032 0.0041 0.0568 H7597 (HCM) None
H8282 (HCM) None
c.1157C>T p.Pro386Leu Missense VUS Novel GBD/FH3 24.7 NA NA 0 0 0.0284 Y398 (control) None
c.1189C>T p.Arg397Cys Missense VUS rs760874847 GBD/FH3 20.7 0.091 0.001 0 0 0.0568 S101 (HCM) MYBPC3,p.Gln469Ter
H7177 (HCM) MYH7, p.Arg1045His
c.1286+2delT NA Spicing Pathogenic Novel Ex 0 0 0.1136 H8306 (HCM) None
H7571 (HCM) None
H7147 (HCM) None
H7104 (HCM) None
c.1309C>T p.Gln437Ter Nonsense LP Novel Ex 35 NA NA 0 0 0.0284 H7115 (HCM) None
c.1552G>A p.Val518Met Missense VUS Novel Ex 25.7 NA NA 0 0 0.0284 H1260 (HCM) MYBPC3, p.Asp1091Gly
c.1580C>T p.Ser527Phe Missense VUS Novel Ex 25.5 NA NA 0 0 0.0284 H8136 (HCM) MYH7, p.Leu832Phe
c.1640A>C p.Glu547Ala Missense VUS Novel Ex 23.7 NA NA 0 0 0.0284 H8194 (HCM) MYBPC3, p.Glu611fs
c.1703G>T p.Arg568Leu Missense VUS Novel Ex 20.9 NA NA 0 0 0.0284 H7327 (HCM) None
c.1733T>A p.Phe578Tyr Missense VUS Novel 19.2 NA NA 0 0 0.0284 Y5332 (control) None
c.1924G>A p.Glu642Lys Missense VUS Novel CC 26.2 0.005 0.979 0 0 0.0284 S099 (HCM) MYH7, p.Gly823Glu
c.2077C>T p.Arg693Trp Missense VUS rs533572045 DID 29.1 0.0 0.292 0.0064 0 0.0284 Y2722 (control) None
c.2078G>A p.Arg693Gln Missense VUS rs148866621 DID 23.2 0.083 0.001 0.0096 0.0087 0.0284 H7520 (HCM) MYBPC3,p.Glu542Lys
c.2090G>A p.Arg697Gln Missense VUS rs553341694 DID 23.2 0.006 0.811 0.0065 0.0095 0.0284 H8315 (HCM) None
c.2429G>T p.Gly810Val Missense VUS Novel DID 22.7 0.02 0.022 0 0 0.0284 H1341 (HCM) None
c.2584G>A p.Asp862Asn Missense VUS rs544119818 DID 21.1 0.671 0.002 0.0032 0.0043 0.0568 H8819 (HCM) None
HT020 (HCM) MYH7, p.Arg663His
c.2746T>G p.Ser916Ala Missense VUS Novel DID 20.8 0.091 0.711 0 0 0.0568 H1424 (HCM) None
T903 (control) None
c.2824G>C p.Glu942Gln Missense VUS rs779000457 DID 27.1 0.016 0.986 0.0025 0.0035 0.0284 H8818 (HCM) MYBPC3, p.Tyr842Ter
c.2837G>A p.Ser946Asn Missense VUS Novel DID 15.46 0.247 0.058 0 0 0.0284 S122 (HCM) MYH7, p.Ile263Thr
c.2954C>A p.Ala985Asp Missense VUS Novel DID 25.9 0.003 0.996 0 0 0.0284 B014 (control) None
c.3005A>T p.Glu1002Val Missense VUS Novel DID 26.9 0.003 0.408 0 0 0.0284 H1253 (HCM) None
c.3412T>C p.Ser1138Pro Missense VUS Novel FH2 23.1 0.071 0.101 0 0 0.0284 HT033 (HCM) None
c.3478G>A p.Ala1160Thr Missense VUS rs746707013 FH2 24.6 0.004 0.777 0.0032 0 0.0284 Y3909 (control) None
c.3587C>G p.Thr1196Arg Missense VUS Novel FH2 25.2 0.01 0.999 0 0 0.0284 Y6233 (control) None
c.3624G>C p.Gln1208His Missense VUS Novel FH2 24.2 0.001 0.909 0 0 0.0284 H8258 (HCM) None
c.3796A>G p.Ile1266Val Missense VUS Novel FH2 25.2 0.276 0.028 0 0 0.0284 H8911 (HCM) MYH7, p.Lys1485Arg
c.4270T>A p.Tyr1424Asn Missense VUS rs753641918 FH2 25.1 0.314 0.003 0.0012 0.0017 0.0568 H8004 (HCM) None
T303 (control) None
c.4586C>T p.Pro1529Leu Missense VUS Novel 18.4 0.342 0.052 0 0 0.0284 Y1615 (control) None
c.4702C>T p.Arg1568Cys Missense VUS rs770836110 DAD 28.1 0.187 0.917 0.0016 0.0008 0.0284 A2015 (control) None
c.4787T>C p.Leu1596Ser Missense VUS Novel DAD 24.1 0.0 0.994 0 0 0.0284 Y4609 (control) None

CADD indicates combined annotation‐dependent depletion score (phred; v1.3; August 2015) 21 ; CC, coiled‐coiled; DAD, diaphanous autoregulation domain; DID, diaphanous autoinhibitory domain; Ex, exclusively cardiac isoform; ExAC, Exome Aggregation Consortium (http://exac.broadinstitute.org); FH2, formin homology 2 domain; FHOD3, formin homology 2 domain‐containing 3; GBD/FH3, GTPase‐binding domain/formin homology 3 domain; GnomAD, Genome Aggregation (https://gnomad.broadinstitute.org); HCM, hypertrophic cardiomyopathy; LP, likely pathogenic; MAF, minor allele frequency; NA, not available; Polyphen, polymorphism phenotyping v2 (September 2014) 23 ; SIFT, sorting intolerant from tolerant (computed from ENSEMBL 55; September 2014) 22 ; SNP, single nucleotide polymorphism; and VUS, variants of uncertain significance.

*

Determined according to criteria in Table S1.