Table 2.
Mutational spectrum in MYBPC3, MYH7, and TNNT2 in Egyptian HCM cohort
| Genea | Ex | Mutation name In protein level | Mutation name in coding DNA level (cDNA) | Mutation type | Domain | Mode of mutation in CpG site | No. of patient (IDs) | Novelty N = novel, R = reported [Ref] (allele freq −EVS)d |
|---|---|---|---|---|---|---|---|---|
| MYBPC3 | 2 | Val94Ala | c.281T > C | Missense | C0 (cardiac-specific region) | – | 1 (P23) | N |
| MYBPC3 | 3 | Pro102Leu | c.305C > T | Missense | Binding site to cardiac actin | – | 2 (P19, PA69) | N |
| MYBPC3 | 4 | Ser139X | c.416C > G | Nonsense | Binding site to cardiac actin | – | 3 (P46, PA15, PU3) | N |
| MYBPC3 | 5 | Arg177His | c.530G > A | Missense | C1 (Ig-like C2-type 1) | CG > A | 1 (P62) | (0.003) |
| MYBPC3 | 5 | Ala179GlnfsX59 | c.534_541del | Frameshift | C1 (Ig-like C2-type 1) | NA | 3 (PA25, PA52, PA46) | N |
| MYBPC3 | 5 | Trp196X | c.587G > A | Nonsense | C1 (Ig-like C2-type 1) | – | 1 (PA19) | N |
| MYBPC3 | 5 | Trp196X | c.588G > A | Nonsense | C1 (Ig-like C2-type 1) | – | 1 (PA18) | N |
| MYBPC3 | 5 | Ala216Thr | c.646G > A | Missense | C1 (Ig-like C2-type 1) | CG > A | 1 (PA64) | R [17] |
| MYBPC3 | 6 | Glu258Lys | c.772G > A | Missense | MYBP-C motif (phosphorylation site) | CG > A | 2 (PA59, PU10) | R [18] |
| MYBPC3 | 9 | Ser296ThrfsX4 | c.887del(G) | Frameshift | MYBP-C motif (phosphorylation site) | NA | 1 (PA90) | N |
| MYBPC3 | 12 | Glu319Ala | c.956A > C | Missense | MYBP-C motif (phosphorylation site) | – | 1 (PA33) | N |
| MYBPC3 | 12 | Tyr333X | c.999C > A | Nonsense | MYBP-C motif (phosphorylation site) | A < CGc | 1 (P69) | N |
| MYBPC3 | 15 | Cys436X | c.1308C > A | Nonsense | C2 (Ig-like C2-type 2) | A < CGc | 1 (PA60) | N |
| MYBPC3 | 15 | Glu441Lys | c.1321G > A | Missense | C2 (Ig-like C2-type 2) | CG > A | 4 (PA38, PA63, PU12, PA123) | R [19] |
| MYBPC3 | 15 | Thr445Met | c.1334C > T | Missense | C2 (Ig-like C2-type 2) | T < CG | 1 (PA53) | N |
| MYBPC3 | 16 | Arg470Pro | c.1409G > C | Missense | C3 (Ig-like C2-type 3) | CG > Cc | 1 (P55) | N |
| MYBPC3 | 16 | Phe473_Glu474del | c.1418_1423del | In-frame | C3 (Ig-like C2-type 3) | NA | 1 (PA80) | N |
| MYBPC3 | 17 | Asp506ThrfsX7 | c.1516del (G) | Frameshift | C3 (Ig-like C2-type 3) | NA | 3 (P70, P62, P63) | N |
| MYBPC3 | 17 | Gly507Arg | c.1519G > A | Missense | C3 (Ig-like C2-type 3) | CG > A | 1 (PA53) | R [20] |
| MYBPC3 | 17 | Asn515Asp | c.1543A > G | Missense | C3 (Ig-like C2-type 3) | – | 1 (PA48) | N |
| MYBPC3 | 18 | Ala558lysfsX9 | c.1672_1673del | Frameshift | C4 (Ig-like C2-type 4) | NA | 1 (P48) | N |
| MYBPC3 | 19 | Glu619Lys | c.1855G > A | Missense | C4 (Ig-like C2-type 4) | CG > A | 2 (P48 ,P76) | R [21] |
| MYBPC3 | 23 | Ile769ThrfsX53 | c.2306del(T) | Frameshift | C5 (Ig-like C2-type 5) | NA | 1 (PA32) | N |
| MYBPC3 | 24 | Val771Met | c.2311G > A | Missense | C6 (fibronectin type-III 1) | CG > A | 1 (PA26) | R [22] |
| MYBPC3 | 25 | Glu832Gly | c.2495A > G | Missense | C6 (fibronectin type-III 1) | – | 2 (P4, P92) | N |
| MYBPC3 | 25 | Arg845Pro | c.2534G > C | Missense | C6 (fibronectin type-III 1) | CG > Cc | 2 (P4, P92) | N |
| MYBPC3 | 27 | Arg943X | c.2827C > T | Nonsense | C7 (fibronectin type-III 2) | T < CG | 1 (PA87) | R [23] |
| MYBPC3 | 28 | Leu993Phe | c.2977C > T | Missense | C8 (Ig-like C2-type 6) | – | 1 (PA16) | N |
| MYBPC3 | 30 | Trp1098X | c.3293G > A | Nonsense | C9 (fibronectin type-III 3) | – | 4 (PA6, PA42, PA56,PA93) | R [24] |
| MYBPC3 | 31 | Arg1138Cys | c.3412C > T | Missense | C9 (fibronectin type-III 3) | T < CG | 1 (PU11) | (0.0002) |
| MYBPC3 | 32 | Glu1179Lys | c.3535G > A | Missense | Connection between C9 and C10 | CG > A | 1 (PA51) | R [25] |
| MYBPC3 | 33 | Glu1239del | c.3715_3717del | In-frame | C10 (Ig-like C2-type 7) | NA | 1 (P39) | N |
| MYBPC3 | 33 | Thr1256AsnfsX10 | c.3766dup.(A) | Frameshift | C10 (Ig-like C2-type 7) | NA | 1 (P36) | N |
| MYH7 | 6 | Glu170Lys | c.508G > A | Missense | Myosin head | – | 1 (P28) | N |
| MYH7 | 9 | Arg249Gln | c.746G > A | Missense | Myosin head | CG > A | 1 (PA55) | R [26] |
| MYH7 | 10 | Leu267Val | c.799C > G | Missense | Myosin head | – | 1 (PA26) | N |
| MYH7 | 11 | Asp309Asn | c.925G > A | Missense | Myosin head | CG > A | 1 (PA8) | N |
| MYH7 | 12 | Glu379Lys | c.1135G > A | Missense | Myosin head | – | 1 (P26) | N |
| MYH7 | 13 | Asp394Glu | c.1182C > A | Missense | Myosin head | – | 1 (PA54) | N |
| MYH7 | 14 | Arg453Cys | c.1357C > T | Missense | Myosin head | T < CG | 1 (P79) | R [27] |
| MYH7 | 15 | Asn471Ser | c.1412A > G | Missense | Myosin head | – | 1 (PA58) | N |
| MYH7 | 15 | Gln498Arg | c.1493A > G | Missense | Myosin head | – | 1 (PA13) | N |
| MYH7 | 18 | Arg663Cys | c.1987C > T | Missense | Myosin head | T < CG | 1 (P8) | R [28] |
| MYH7 | 19 | Gly716Ala | c.2147G > C | Missense | Myosin head | – | 1 (PA30) | N |
| MYH7 | 19 | Arg719Gln | c.2156G > A | Missense | Myosin head | CG > A | 2 (PA4, P67) | R [29] |
| MYH7 | 20 | Pro731Leu | c.2192C > T | Missense | Myosin head | – | 1 (P29) | R [30] |
| MYH7 | 21 | Ala797Thr | c.2389G > A | Missense | IQ domain | CG > A | 1 (P16) | R [31] |
| MYH7 | 22 | Arg819Gln | c.2456G > A | Missense | Connection between head and coiled coil | CG > A | 1 (P73) | N |
| MYH7 | 22 | Lys847del | c.2539_2541del | In-frame | Myosin coiled coil | NA | 1 (P53) | R [13] |
| MYH7 | 23 | Glu927Lys | c.2779G > A | Missense | Myosin coiled coil | – | 1 (PA12) | R [32] |
| MYH7 | 23 | Met932Lys | c.2795T > A | Missense | Myosin coiled coil | – | 1 (P56) | R [33] |
| MYH7 | 25 | Glu1056Asp | c.3168G > C | Missense | Myosin coiled coil | – | 1 (PA57) | N |
| MYH7 | 35 | Arg1662His | c.4985G > A | Missense | Myosin coiled coil | CG > A | 1 (PU1) | (0.00008) |
| MYH7 | 39 | Ser1924AlafsX9 | c.5769del (G) | Frameshift | Myosin coiled coil | NA | 3 (P37, PA24, P85) | N |
| TNNT2 | 10 | Arg92Trp | c.274C > T | Missense | Troponin T chain | T < CG | 1 (P45) | R [34] |
| TNNT2 | 10 | Arg92Gln | c.275G > A | Missense | Troponin T chain | CG > A | 2 (P34, P98) | R [35] |
| TNNT2 | 11 | Asn142Tyr | c.424A > T | Missense | Troponin T chain | – | 1 (P22) | N |
| TNNT2 | 16 | Asn262Asp | c.784A > G | Missense | Troponin T chain | – | 1 (PA89) | N |
| TNNT2 | 16 | Asn269Lys | c.807C > A | Missense | Troponin T chain | A < CGc | 2 (P47, PA66) | N |
| TNNT2 | 17 | Arg278Leu | c.833G > T | Missense | Troponin T chain | CG > Tc | 1 (PU7) | N |
Caps and italics are names of genes according to HUGO nomenclature of genes
aGenBank reference: MYBPC3:NM_000256.3; MYH7: NM_000257.2; TNNT2: NM_001001430.1
bUniprot reference: cardiac myosin-binding protein C: Q14896; myosin heavy chain 7: P12883; cardiac troponin T: P45379; IQ domain: calmodulin binding domain: http://www.uniprot.org/uniprot/Q14896,P12883,P45379
cCpG substitution by a mutagenic mutation other than deamination of methylated cytosine to thymine
dAllele frequency obtained from Exome Variant Server (EVS) of Exome Sequencing Project: http://evs.gs.washington.edu/EVS/) [36]. Mutations in bold were reported in EVS