Circulation Journal Supplementary File Official Journal of the Japanese Circulation Society http://www.j-circ.or.jp Circ J 2013; 77: 2358 – 2365 Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 Mutations in Sporadic Hypertrophic Cardiomyopathy Lucía Núñez, PhD; Juan Ramón Gimeno-Blanes, MD, PhD; María Isabel Rodríguez-García, BSc, PhD; Lorenzo Monserrat, MD, PhD; Esther Zorio, MD; Caroline Coats, BSc; Christopher G. McGregor, MD; Juan Pedro Hernandez del Rincón, MD, PhD; Alfonso Castro-Beiras, MD, PhD; Manuel Hermida-Prieto, BSc, PhD

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Table S1. Mutations Previously Described in the Literature Familial studies: FH Index Presence of Mutation CA/CAN/CNS/ Functional studies of Other information Ref. cases other mutations NCA/NCNA/OM SCD MYBPC3 A216T 2 Not performed Not performed Y S1, S2 V219L 2 Performed (NI) Not performed S3, S4 E258K 12 Performed: The dramatic change in Y MYBPC3-R834W, Founder effect S5–S13 7/2/0/0/1/4/1 charge associated with MYBPC3-L1200P, suggested the E258K must be the MYH7-R869H, Could affect the splice responsible of the damage. TNNI3-A86fs site (exon 6 skipped) Haploinsufficiency seem and could produce to be the procedure premature termination implicated to cause the Structure: surface of disease. the C1 domain structure G278E 4 Not performed Not performed S14–S17 IVS14–13G>A 2 Performed: Not performed S18, S19 1/0/0/0/0/0 R495W 3 Performed: Not performed Y Hotspots: R495W/ S2, S20–S22 1/2/0/0/0/0 R495Q/R495G R502W 54 Performed: May only be degraded Y MYBPC3-S858N, Hotspots: R502W/ S1, S3, S4, 17/5/15/0/14/4 by the UPS MYBPC3-E542Q, R502Q S10, MYBPC3-G148R, S14–S16, MYH7-D587N S22–S29 IVS17+4A>T 2 Performed (NI) Haploinsufficiency Y TNNT2-R286H S4, S10, S24, seems to be the proce- S28 dure implicated A833T 12 Performed: Haploinsufficiency Y MYBPC3-IVS23- Founder effect S3, S5, S16, 8/3/0/2/2/1 seems to be the proce- 2delA, suggested S30–S35 dure implicated MYH7-L390V, Hotspots: A833T, May disrupt the bonds TNNT2-R286H A833V between EF-Motif 6 and Found the mutated BC-Motif 7, resulting in allele in 2 of 200 incorrect packing and healthy controls assembly of MyBPC IVS23–2A>G 3 Not performed Not performed S3, S6, S36 R1022P 5 Performed: Not performed MYH7-A868P, S2, S16, 3/0/0/2/0/0 MYBPC3-R810L S17, S37 IVS30+5G>C 1 Performed: Not performed S38 8/1/0/0/7/0 MYH7 V606M 18 Performed: Show defects in the Y MYPN-P1112L Associated with benign S14, S16, 21/2/0/0/7/0 ATPase activity. effect S17, S24, S39–S62 R719Q 18 Performed: Large effect on phos- Y MYBPC3-V158M, Hotspots: R719Q/ S1, S3, 6/2/0/0/0/3 phorylation-dependent MYBPC3-R273H, R719W/R719P S14–S17, regulation MYH7-T1513S S24, S25, Could have an effect on S28, S50, motility S51, S53, Presented moderately S61, reduced level of force S63–S75 Alters gene transcription A797T 21 Performed: Not performed Y Milder clinical disease S4, S6, S55, 18/22/0/0/31/0 course S67, S69, Founder mutation S76–S82 K847E 7 Performed (NI) Not performed Favorable prognosis S4, S83 K847del 4 Not performed Not performed S69, S84–S85 E1356K 5 Not performed Thermodynamically Y S16, S37, destabilized the protein S69, and decreased the S86–S88 ability of the protein to form filaments TNNT2 R278C 7 Performed: Not performed Y Hotspots: R278C/ S38, 3/0/0/0/0/0 R278P S89–S92 TNNI3 R186Q 11 Performed: Not performed Y S14, S16, 5/6/0/0/8/0 S17, S75, S93–S97 CA, carriers affected; CAN, carriers non-affected; CNS, carriers non-evaluated clinically; FH, family history; NCA, non-carriers affected; NCNA, non-carriers non-affected; NI, non-specific information given; OM, carriers of other mutations; SCD, sudden cardiac death; UPS, ubiq- uitin-proteosome system.

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