Table 1 Variants in CAPN3 gene found in LGMDR1 patients, in-silico analysis and genotype-phenotype correlation
From: Identification of novel pathogenic variants of Calpain-3 gene in limb girdle muscular dystrophy R1
Genotype-phenotype correlation | Waddling gait; wasting of biceps, triceps and supraspinatus muscle; Calf with EDB (extensor digitorum brevis) muscle and Beevor sign were observed | Waddling gait and scapular winging | Proximal weakness since 2 years | Problems in running since the last 6 years, difficulty in getting up | Difficulty in climbing stairs, getting up from squatting position. Waddling gait, scapular winging and adductor splay sign were observed | Patient needed support during walking, with presence of lordotic posture and was wheelchair bound |
|---|---|---|---|---|---|---|
ACMG criteria and classification | PM1, PM2, PP2, PP3 (Likely pathogenic) | PM1, PM2, PP2, PP3, PP5 (Pathogenic) | PVS1, PM2, PM3, PP3, PP5 & PM1, PM2, PM3, PP2, PP3, PP5 (Pathogenic) | PVS1, PM2, PP3 (Pathogenic) | PM1, PM2, PP2, PP3, PP5 (Pathogenic) | PVS1, PM2, PP3, PP5 (Pathogenic) |
Human Splice Site Finder | Acceptor splice site affected | |||||
Mutation Taster | Disease causing | Disease causing | Disease causing | Disease causing | Disease causing | Disease causing |
Provean | del (-5.318) | del (-5.973) | del (-5.973) | del (-5.973) | ||
PolyPhen | PD (0.929) | PD (1.000) | PD (1.000) | PD (1.000) | ||
Mutation type | Missense | Missense | Splice site variant & missense | Insertion-deletion | Missense | Nonsense |
HGVSp | p.Phe397Leu | p.Asp780His | p.Asp780His | p.Arg490Leufs*87 | p.Asp780His | p.Glu647Ter |
HGVSc | c.1189T > C | c.2338G > C | c.2338G > C & c.2051-1G > T | c.1688delinsTC | c.2338G > C | c.1939G > T |
Genotype | Homo | Homo | Hetero | Homo | Homo | Homo |
Exon | 9 | 22 | 22 & splice site variant | 11 | 22 | 17 |
Gene | CAPN3 | CAPN3 | CAPN3 | CAPN3 | CAPN3 | CAPN3 |
Patient (Age/Sex) | 1 (19/M) | 2 (45/M) | 3 (25/F) | 4 (26/M) | 5 (26/F) | 6 (22/M) |