ClinVar Miner

Submissions for variant NM_000023.4(SGCA):c.100C>T (p.Arg34Cys) (rs758647756)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201165 SCV000255836 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2012-12-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000493338 SCV000332844 pathogenic not provided 2018-07-20 criteria provided, single submitter clinical testing
GeneDx RCV000493338 SCV000581759 likely pathogenic not provided 2017-04-21 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the SGCA gene. The R34C variant has been previously reported in the homozygous state in an individual with severe LGMD2D; parental studies were not performed (Carrie et al., 1997; Eymard et al., 1997). The R34C 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). The R34C 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. This substitution occurs at a position that is conserved across species. Missense variants at the same residue (R34H/L) and in nearby residues (P30L, L31P) have been reported in the Human Gene Mutation Database in association with SGCA-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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