Detection of variants in dystroglycanopathy-associated genes through the application of targeted whole-exome sequencing analysis to a large cohort of patients with unexplained limb-girdle muscle weakness

Johnson, Katherine; Bertoli, Marta; Phillips, Lauren; Töpf, Ana; Van den Bergh, Peter; Vissing, John; Witting, Nanna; Nafissi, Shahriar; Jamal-Omidi, Shirin; Łusakowska, Anna; Kostera-Pruszczyk, Anna; Potulska-Chromik, Anna; Deconinck, Nicolas; Wallgren-Pettersson, Carina; Strang-Karlsson, Sonja; Colomer, Jaume; Claeys, Kristl G.; De Ridder, Willem; Baets, Jonathan; von der Hagen, Maja; Fernández-Torrón, Roberto; Zulaica Ijurco, Miren; Espinal Valencia, Juan Bautista; Hahn, Andreas; Durmus, Hacer; Willis, Tracey; Xu, Liwen; Valkanas, Elise; Mullen, Thomas E.; Lek, Monkol; MacArthur, Daniel G.; Straub, Volker

doi:10.1186/s13395-018-0170-1

Table 3 Suspected pathogenic compound heterozygous variants detected by the MYO-SEQ project in dystroglycanopathy-associated genes

From: Detection of variants in dystroglycanopathy-associated genes through the application of targeted whole-exome sequencing analysis to a large cohort of patients with unexplained limb-girdle muscle weakness

Patient	Gene	Location			Predicted deleteriousness				ClinVar clinical significance	gnomAD allele frequency
Patient	Gene	hg19 co-ordinates	Protein change	Sequence change	SIFT	PolyPhen-2	MutationTaster2	FATHMM	ClinVar clinical significance	gnomAD allele frequency
9	FKRP	chr19:47259533	p.Leu276Ile	c.826C>A	Tolerated	Benign	Disease causing	Damaging	Pathogenic; likely pathogenic	0.001089^a
9	FKRP	chr19:47260091	p.Pro462Ser	c.1384C>T	Damaging	Probably damaging	Disease causing	Damaging	No data	0.000009^a
10	FKTN	chr9:108380248	p.Arg307Ter	c.919C>T	No data	No data	Disease causing	No data	Pathogenic; likely pathogenic	0.000020^a
10	FKTN	chr9:108380249	p.Arg307Gln	c.920G>A	No data	Probably damaging	Disease causing	Damaging	Pathogenic	0.000012^a
11	GMPPB	chr3:49761081	p.Asp27His	c.79G>C	Damaging	Possibly damaging	Disease causing	Damaging	Pathogenic	0.000655
11	GMPPB	chr3:49759490	p.Arg287Trp	c.859C>T	Damaging	Possibly damaging	Disease causing	Tolerated	Pathogenic	0.000094^a
12	GMPPB	chr3:49761081	p.Asp27His	c.79G>C	Damaging	Possibly damaging	Disease causing	Damaging	Pathogenic	0.000655
12	GMPPB	chr3:49759490	p.Arg287Trp	c.859C>T	Damaging	Possibly damaging	Disease causing	Tolerated	Pathogenic	0.000094^a
13	GMPPB	chr3:49760844	p.Met64Ter	c.190delA	No data	No data	No data	No data	No data	0.000000^a
13	GMPPB	chr3:49761081	p.Asp27His	c.79G>C	Damaging	Possibly damaging	Disease causing	Damaging	Pathogenic	0.000655
14	ISPD	chr7:16460782	p.Cys56ValfsTer60	c.165dupG	No data	No data	No data	No data	No data	0.000000^a
14	ISPD	chr7:16415796	p.Ser202Leu	c.605C>T	Damaging	Probably damaging	Disease causing	Damaging	No data	0.000033^a
15	POMK	chr8:42977932	p.Pro322Leu	c.965C>T	Damaging	Probably damaging	Disease causing	Tolerated	No data	0.000004^a
15	POMK	chr8:42958827	p.Arg46Ter	c.136C>T	No data	No data	Disease causing	No data	No data	0.000180^a
16	POMK	chr8:42977932	p.Pro322Leu	c.965C>T	Damaging	Probably damaging	Disease causing	Tolerated	No data	0.000004^a
16	POMK	chr8:42958827	p.Arg46Ter	c.136C>T	No data	No data	Disease causing	No data	No data	0.000180^a
17	POMT1	chr9:134381575	p.Pro66Leu	c.197C>T	Damaging	Probably damaging	Disease causing	Damaging	No data	0.000053^a
17	POMT1	chr9:134398412	p.Asp723GlyfsTer8	c.2167dupG	No data	No data	No data	No data	Pathogenic	0.000171^a
18	POMT2	chr14:77753158	p.Arg421Trp	c.1261C>T	Damaging	Probably damaging	Disease causing	Damaging	Likely pathogenic	0.000024^a
18	POMT2	chr14:77762593	p.Thr344Pro	c.1030A>C	Damaging	Probably damaging	Disease causing	Damaging	Uncertain	0.000000^a
19	POMT2	chr14:77746421	p.Leu577ProfsTer8	c.1727dupG	No data	No data	No data	No data	No data	0.000032^a
19	POMT2	chr14:77753158	p.Arg421Trp	c.1261C>T	Damaging	Probably damaging	Disease causing	Damaging	Likely pathogenic	0.000024^a
20	POMT2	chr14:77746421	p.Leu577ProfsTer8	c.1727dupG	No data	No data	No data	No data	No data	0.000032^a
20	POMT2	chr14:77753158	p.Arg421Trp	c.1261C>T	Damaging	Probably damaging	Disease causing	Damaging	Likely pathogenic	0.000024^a
21	POMT2	chr14:77751373	p.Gln499Arg	c.1496A>G	Damaging	Probably damaging	Disease causing	Damaging	No data	0.000000^a
21	POMT2	chr14:77755120	p.Arg413Pro	c.1238G>C	Damaging	Probably damaging	Disease causing	Damaging	Pathogenic; uncertain	0.000028^a
23	POMT2	chr14:77744748	p.Gly705GlufsTer31	c.2114_2135delGAATCCTGAGCCTGCTCCTGGG	No data	No data	No data	No data	No data	0.000000^a
23	POMT2	chr14:77769283	p.Thr184Met	c.551C>T	No data	Probably damaging	Disease causing	Damaging	Pathogenic	0.000007^a
24	POMT2	chr14:77772712	p.Tyr136His	c.406T>C	Damaging	Probably damaging	Disease causing	Damaging	No data	0.000000^a
24	POMT2	chr14:77745107	p.Tyr666Cys	c.1997A>G	Damaging	Probably damaging	Disease causing	Damaging	Pathogenic; likely pathogenic	0.000061^a
25	POMT2	chr14:77767432	ESS	c.816+1G>A	No data	No data	Disease causing	No data	No data	0.000004^a
25	POMT2	chr14:77778319	p.Phe102Leu	c.306C>A	Damaging	Probably damaging	Disease causing	Damaging	No data	0.000000^a
26	POMT2	chr14:77750156	p.His546Pro	c.1637A>C	No data	No data	Disease causing	No data	No data	0.000007^a
26	POMT2	chr14:77769277	p.Cys186Tyr	c.1654-5T>G	Tolerated	Possibly damaging	Disease causing	Damaging	No data	0.000000^a
27	POMT2	chr14:77746811	ExtSS	c.1654-5T>G	No data	No data	No data	No data	No data	0.000000^a
27	POMT2	chr14:77765843	p.Leu293His	c.878T>A	No data	Probably damaging	Disease causing	Damaging	No data	0.000000^a

ESS essential splice site, ExSS extended splice site
^aNot reported in homozygosity in gnomAD

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