ClinVar Miner

Submissions for variant NM_000232.5(SGCB):c.-10_22dup (p.Ala8fs)

dbSNP: rs1553940963
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538793 SCV000642375 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-11-30 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the SGCB gene. It may leave the encoded amino acid sequence of the SGCB protein unchanged or may create a premature translational stop signal (p.Ala8Glyfs*22). This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 12746421, 25862795; Invitae). This variant is also known as c.-10_22dup (Non-coding), –22+10dup, and PTC+25aa. ClinVar contains an entry for this variant (Variation ID: 466601). Studies have shown that this variant alters SGCB gene expression (PMID: 25862795). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001778998 SCV002015074 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy 2021-10-01 criteria provided, single submitter clinical testing Variant summary: SGCB c.-10_22dup32 is located in the untranslated mRNA region upstream and the coding region including the initiation codon.The variant was absent in 37246 control chromosomes (gnomAD v2), however, it is found in 9/150846 controls in gnomAD v3. c.-10_22dup32 has been reported in the literature in multiple individuals affected with mild Limb-Girdle Muscular Dystrophy in homozygous state (Boito_2003, Semplicini_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. This variant is predicted to result in p.Ala8Glyfs*22 if the first initiation codon is utilized for translation. However, biochemical data of residual sarcoglycan expression in skeletal muscle and mild phenotype in variant carriers suggest that the second initiation codon in the mutant gene may also be utilized, which results in a normal protein (Semplicini_2015). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Although this variant has been found in mutliple patients, due to lack of functional evidence, the variant was classified as likely pathogenic.
Revvity Omics, Revvity RCV000538793 SCV003808160 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-04-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV000538793 SCV004200994 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-06-17 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000596558 SCV000700913 uncertain significance not provided 2015-08-21 flagged submission clinical testing

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