Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies

Table 2 Summary of genetic data and pathogenicity interpretation of DMD variants according to the standard guidelines

Patient number	cDNA variant	Absence of mRNA and protein studies			Evidence derived from mRNA and protein studies
Patient number	cDNA variant	Predicted protein variant	Evidence of pathogenicity	Pathogenicity	Confirmed RNA variant	Confirmed protein variant	Confirmed variant type	Exon	Dystrophin domain	Variant frameness	Evidence of pathogenicity	Pathogenicity
P1	c.2380G > C	p.(Glu794Gln)	PM1, PM2, PP3	VUS	r.[2380g > c,2293_2380del,2374_2380del]	p.[Glu794Gln,Ala765Argfs15,Val792Argfs15]	Splicing	19	R4	Inframe and frameshift	PVS1, PS3, PM1, PM2, PP3	P
P2	c.4977C > G	p.(Asn1659Lys)	PM1, PM2, PP4	VUS	r.4973_5025del	p.Ser1658Argfs*10	Splicing	35	R12	Frameshift	PVS1, PS3, PM1, PM2, PP4	P
P3	c.5444A > G*	p.(Asp1815Gly)	PS3, PM2, PP3, PP4	LP	r.5444_5448del	p.Asp1815Glufs*2	Splicing	38	R14	Frameshift	PVS1, PS3, PM2, PP3, PP4	P
P4	c.329T > C	p.(Leu110Ser)	PM1, PM2, PP3	VUS	r.329u > c	p.Leu110Ser	Missense	6	ABD:CH1	Inframe	PS3, PM1, PM2, PP3	LP
P5	c.442A > C*	p.(Thr148Pro)	PM1, PM2, PP3, PP4, PP5	LP	r.442a > c	p.Thr148Pro	Missense	6	ABD:CH2	Inframe	PS3, PM1, PM2, PP3, PP4, PP5	P
P6	c.511G > C*	p.(Ala171Pro)	PM1, PM2, PP3, PP5	LP	r.511g > c	p.Ala171Pro	Missense	6	ABD:CH2	Inframe	PS3, PM1, PM2, PP3, PP5	P
P7	c.1649G > C	p.(Arg550Pro)	PM1, PM2, PP3	VUS	r.1649g > c	p.Arg550Pro	Missense	14	R2	Inframe	PS3, PM1, PM2, PP3	LP
P8	c.4760T > C	p.(Leu1587Pro)	PM1, PM2, PP3	VUS	r.4760u > c	p.Leu1587Pro	Missense	34	R12	Inframe	PS3, PM1, PM2, PP3	LP
P9	c.5192T > G	p.(Val1731Gly)	PM1, PM2	VUS	r.5192u > g	p.Val1731Gly	Missense	37	R13	Inframe	PS3, PM1, PM2	LP

^*Variants have been previously reported [15, 25, 26]. Variants were described in relation to the coding DNA reference sequence NM_004006.2, RNA reference sequence NM_004006.2, and protein reference sequence NP_003997.1. ABD, actin-binding domain; CH1-2, calponin homology; R1-24, spectrin-like repeats; VUS, variant of uncertain significance; LP, likely pathogenic; P, pathogenic; PVS1, very strong evidence; PS, strong evidence; PM, moderate evidence; PP, supporting evidence

ISSN: 1750-1172