Coding Sequence Mutations Identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 Patients with Familial or Idiopathic Dilated Cardiomyopathy

Ray E. Hershberger; Sharie B. Parks; Jessica D. Kushner; Duanxiang Li; Susan Ludwigsen; Petra Jakobs; Deirdre Nauman; Donna Burgess; Julie Partain; Michael Litt

doi:10.1111/j.1752-8062.2008.00017.x

Table 2

Nonsynonymous nucleotide alterations in six FDC/IDC genes.

Gene/Proband	Exon	Nucleotide change*	Amino acid change	Conservation^†	Segregation^\|	Disease‐associated?	Diagnosis, FDC^¶ or IDC^∥	Previously reported cardiovascular disease	Reference
A. MYH7, β‐myosin heavy chain
A.1#	8	4231C>T	Arg237Trp	Yes		Possibly	FDC
A.2	23	11900G>C	Val964Leu	Yes		Possibly	FDC
A.3	23	11919C>T	Ala970Val	Yes		Possibly	FDC
A.4	25	13547C>T	Arg1045Cys	Yes		Possibly	IDC
A.5	26	14831G>T	Asp1096Tyr	Yes		Possibly	FDC
A.6	26	14831G>T	Asp1096Tyr	Yes		Possibly	IDC
A.7	30	17536C>T	Arg1359Cys	Yes		Possibly	IDC
A.8	32	18666C>T	Arg1500Trp	Yes	Yes	Likely	FDC	DCM	34
A.9	34	19738G>A	Glu1619Lys	Yes		Possibly	FDC
A.10	35	20125G>A	Val1691Met	Yes		Possibly	FDC	HCM	35
A.11^‡	37	20709G>C**	Gly1808Ala	Yes		Likely	FDC
A.12	39	21994C>G	His1901Gln	Yes		Possibly	FDC	Skeletal myopathy	36
A.13	38	21766G>A	Arg1863Gln	Yes		Possibly	FDC
B. TNNT2, cardiac troponin T
B.1	11/10	13712C>G	Arg134Gly	Yes	Yes	Likely	FDC
B.2	11/10	13763C>T**	Arg151Cys	Yes		Likely	IDC
B.3	12/11	14679G>A	Arg159Gln	Yes		Possibly	IDC
B.4	13	16080C>T	Arg205Trp	Yes		Likely	IDC	DCM	18
B.5	13	16096_16098delAGA	Lys210del	N/A		Likely	FDC	DCM	10, 11, 18, 37
B.6	13	16096_16098delAGA	Lys210del	N/A	Yes	Likely	FDC	DCM	10, 11, 18, 37
B.7	13	16096_16098delAGA	Lys210del	N/A	Yes	Likely	FDC	DCM	10, 11, 18, 37
B.8	13	16096_16098delAGA	Lys210del	N/A	Yes	Likely	FDC	DCM	10, 11, 18, 37
B.9^‡	14	16742G>T	Glu244Asp	Yes		Possibly	IDC	HCM	38
C. SCN5A, cardiac sodium channel
C.1	6	36665C>T	Ser216Leu	Yes		Possibly	IDC	Long QT	39
C.2	6	36665C>T	Ser216Leu	Yes		Possibly	IDC	Long QT
C.3	6	36683G>A	Arg222GLN	Yes	Yes	Likely	FDC
C.4	12	46439G>A	Arg526His	Yes	No	Unlikely	IDC	Brugada Syndrome	40
C.5^§	12	46577C>A	Ala572Asp	No	No	Unlikely	FDC	Long QT	41
C.6	13	51466C>T	Pro648Leu	Yes		Possibly	FDC	Long QT	42
C.7^†	28	99599T>C	Ile1835Thr	Yes	Yes	Likely	FDC
C.8	28	100108C>G	Pro2005Ala	Yes		Possibly	IDC	Long QT	43
D. TCAP, titin‐cap or telethonin
D.1	1	1630G>A	Arg18Gln	Yes		Possibly	IDC
D.2	2	1968G>A	Glu49Lys	Yes		Possibly	IDC
D.3^∥∥	2	2244C>G	Pro141Ala	Yes	No	Unlikely	IDC
E. LDB3, limb domain‐binding 3
E.1	8	41461G>A	Ala371Thr	No		Unlikely	FDC
E.2	12	57781G>A	Ala698Thr	Yes		Possibly	IDC
E.3#	12	57781G>A	Ala698Thr	Yes		Possibly	FDC
F. CSRP3, cysteine‐ and glycine‐rich protein 3
F.1	3	14108G>A	Gly72Arg	Yes		Possibly	IDC

*Nucleotide numbering is per the SeattleSNPs resequencing service. Amino acid numbering is per previous publications. ^† Human sequence was compared to rat (r) and mouse (m); N/A, not applicable. ^¶Probable FDC was considered FDC, and ^∥possible FDC was considered IDC (see Methods). ^|Segregation means multiple affected carrying mutation and/or multiple nonaffected not carrying mutation; entry left blank because of insufficient clinical data and/or DNA specimens to assess segregation. #A.1 and E.3 is same proband with compound heterozygosity. **Homozygous mutation; Caucasian of Hispanic descent. ^‡African‐American. ^§Proband carries likely disease ‐causing presenilin 2 mutation. ^∥∥Proband carries likely disease‐causing lamin A/C mutation.