ClinVar Miner

Submissions for variant NM_000231.2(SGCG):c.787G>A (p.Glu263Lys) (rs104894423)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000002086 SCV000255841 pathogenic Severe autosomal recessive muscular dystrophy of childhood - North African type 2013-10-21 criteria provided, single submitter clinical testing
Counsyl RCV000002086 SCV000789622 likely pathogenic Severe autosomal recessive muscular dystrophy of childhood - North African type 2017-02-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078408 SCV000232489 pathogenic not provided 2016-10-04 criteria provided, single submitter clinical testing
GeneDx RCV000078408 SCV000518064 pathogenic not provided 2017-06-27 criteria provided, single submitter clinical testing The E263K missense variant in the SGCG gene has been reported previously multiple times in association with LGMD2C (Duncan et al., 2006; DiCapua et al., 2014; Al-Zaidy et al., 2015). Immunostaining of muscle biopsies revealed absent gamma-sarcoglycan staining (Duncan et al., 2006; Al-Zaidy et al., 2015). It has been suggested that E263K is a founder mutation in the Puerto Rican population (Duncan et al., 2006; DiCapua et al., 2014; Al-Zaidy et al., 2015). The E263K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. We interpret E263K as a pathogenic variant.
Invitae RCV000002086 SCV000634390 pathogenic Severe autosomal recessive muscular dystrophy of childhood - North African type 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 263 of the SGCG protein (p.Glu263Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs104894423, ExAC 0.006%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with severe limb-girdle muscular dystrophy (LGMD) (PMID: 18285821). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease.  Additionally this variant has been reported as homozygous in several individuals affected with LGMD (PMID: 25802879, 24534832, 16832103, 27708273). ClinVar contains an entry for this variant (Variation ID: 2009). Experimental studies have shown that this missense variant leads to mislocalization of the SGCG protein (PMID: 22095924). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002086 SCV000022244 pathogenic Severe autosomal recessive muscular dystrophy of childhood - North African type 2006-07-11 no assertion criteria provided literature only

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