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Table 3 Summary of genetic data and clinical interpretation of novel candidate variants detected in SGCA, SGCB, and SGCG according to the 2015 ACMG-AMP guidelines [19]

From: Clinical and genetic spectrum of sarcoglycanopathies in a large cohort of Chinese patients

Patients

Gene

c.DNA position

Exon

Effect on protein

Type of variants

Location of mutation allele

Parental derivation

Variants pathogenicity

Evidence of pathogenicity

P1

SGCA

c.101G > Aa

Exon 2

p.R34H

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.218C > Gb

Exon 3

p.P73R

Missense

Extracellular

Paternal

Likely pathogenic

PM1, PM2, PM3, PP1, PP3, PP4

 

PMP22

Exons 1–5 duplicationa

Exons 1–5

–

Large duplication

–

NA

Pathogenic

 

P2

SGCA

c.158-10_160delb

Intron 2, Exon 3

–

Splicing#

Extracellular

Maternal

Likely pathogenic

PM2, PM3, PP1, PP3, PP4

 

SGCA

c.662G > Aa

Exon 6

p.R221H

Missense

Extracellular

Paternal

Pathogenic

 

P3

SGCA

c.662G > Aa

Exon 6

p.R221H

Missense

Extracellular

NA

Pathogenic

 

P4

SGCA

c.313-2A > Ga

Intron 3

NA

Splicing

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.95 T > Ca

Exon 2

p.V32A

Missense

Extracellular

Paternal

Pathogenic

 

P5

SGCA

c.424A > Ga

Exon 5

p.S142G

Missense

Extracellular

NA

Pathogenic

 

P6

SGCA

c.889delCa

Exon 7

p.L298Cfs*23

Frameshift

TM

Maternal

Pathogenic

 
 

SGCA

c.292C > Ta

Exon 3

p.R98C

Missense

Extracellular

Paternal

Pathogenic

 

P7

SGCA

c.409G > Ca

Exon 5

p.E137Q

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.95 T > Ca

Exon 2

p.V32A

Missense

Extracellular

Paternal

Pathogenic

 

P8

SGCA

c.661C > Ta

Exon 6

p.R221C

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.320C > Ta

Exon 4

p.A107V

Missense

Extracellular

Paternal

Pathogenic

 

P9

SGCA

c.233_234delinsGAa

Exon 3

p.Y78*

Nonsense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.371 T > Ca

Exon 4

p.I124T

Missense

Extracellular

Paternal

Pathogenic

 

P10

SGCA

Exons 1–7 duplicationb

Exons 1–7

–

Large duplication

Singal peptide + Extracellular + TM + Intracellular

Maternal

Pathogenic

PVS1, PM3, PP1, PP4

 

SGCA

c.229C > Ta

Exon 3

p.R77C

Missense

Extracellular

Paternal

Pathogenic

 

P11

SGCA

Exons 4–8 deletionb

Exons 4–8

–

Large deletion

Extracellular + TM + Intracellular

Maternal

Pathogenic

PVS1, PM3, PP1, PP4

 

SGCA

c.234C > Ab

Exon 3

p.Y78*

Nonsense

Extracellular

Paternal

Pathogenic

PVS1, PM2, PP4

P12

SGCA

c.956 + 2 T > Ca

Intron 7

–

Splicing

Intracellular

Maternal

Pathogenic

 
 

SGCA

c.662G > Aa

Exon 6

p.R221H

Missense

Extracellular

Paternal

Pathogenic

 

P13

SGCA

c.427C > Tb

Exon 5

p.H143Y

Missense

Extracellular

Maternal

Likely pathogenic

PM2, PM3, PP1, PP3, PP4

 

SGCA

c.229C > Ta

Exon 3

p.R77C

Missense

Extracellular

Paternal

Pathogenic

 

P14

SGCA

c.662G > Aa

Exon 6

p.R221H

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.956G > Ab

Exon 7

p.R319K

Missense

Intracellular

Paternal

Likely pathogenic

PM2, PM3, PP1, PP4

P15

SGCA

Exons 7–8 deletiona

Exons 7–8

–

Large deletion

TM + Intracellular

Maternal

Pathogenic

 
 

SGCA

c.218C > Tb

Exon 3

p.P73L

Missense

Extracellular

Paternal

Likely pathogenic

PM1, PM2, PM3, PP1, PP3, PP4

P16

SGCA

c.1A > Gb (hom)

Exon 1

p.0?

Init-loss

Singal peptide

Maternal/Paternal

Pathogenic

PVS1, PM2, PP1, PP3, PP4

P17

SGCA

c.662G > Aa

Exon 6

p.R221H

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.95 T > Ca

Exon 2

p.V32A

Missense

Extracellular

Paternal

Pathogenic

 

P18

SGCA

c.409G > Aa

Exon 5

p.E137K

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCA

c.687delTb

Exon 6

p.L230Cfs*18

Frameshift

Extracellular

Paternal

Pathogenic

PVS1, PM2, PM3, PP1, PP4

P19

SGCB

c.551A > Ga

Exon 4

p.Y184C

Missense

Extracellular

Maternal

Pathogenic

 
 

SGCB

Exons 5–6 deletionb

Exons 5–6

–

Large deletion

Extracellular

Paternal

Pathogenic

PVS1, PM3, PP1, PP4

P20

SGCB

c.334C > Ta

Exon 3

p.Q112*

Nonsense

Extracellular

Paternal

Pathogenic

 

P21

SGCB

c.29_33delAACAGb (hom)

Exon 1

p.E10Afs*13

Frameshift

Intracellular

Maternal/Paternal

Pathogenic

PVS1, PM2, PP1, PP4

P22

SGCB

c.273_292delb (hom)

Exon 3

p.I92*

Frameshift

TM

NA

Pathogenic

PVS1, PM2, PP4

P23

SGCB

c.29_33delAACAGb

Exon 1

p.E10Afs*13

Frameshift

Intracellular

Maternal

Pathogenic

PVS1, PM2, PP1, PP4

 

SGCB

c.366_367delTTb

Exon 3

p.Y123*

Frameshift

Extracellular

Paternal

Pathogenic

PVS1, PM2, PP1, PP4

P24

SGCB

c.543C > Ab

Exon 4

p.S181R

Missense

Extracellular

Maternal

Likely pathogenic

PS1, PM2, PP3, PP4

P25

SGCG

c.320C > Tb (hom)

Exon 4

p.S107 L

Missense

Extracellular

Maternal/Paternal

Likely pathogenic

PM2, PM3, PP1, PP3, PP4

  1. a, The variants have been previously reported as pathogenic [2, 13, 33,34,35,36,37,38,39,40,41,42]; b, novel variants; #, This mutation most likely affects splicing because it can cause loss of the acceptor splice sites, as confirmed by HSF Matrices and MaxEnt algorithms [30]. Init-loss, initiation codon loss; hom, homozygous; NA not available, TM transmembrane, PVS pathogenic very strong, PS pathogenic strong, PM pathogenic moderate, PP pathogenic supporting; c.158-10_160del, c.158-10_160delCTTCCACCAGCTG; c.273_292del, c.273_292delCATTGGACCAAATGGCTGTG