ClinVar Miner

Submissions for variant NM_000232.5(SGCB):c.544A>C (p.Thr182Pro)

gnomAD frequency: 0.00001  dbSNP: rs751427686
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544134 SCV000642381 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 182 of the SGCB protein (p.Thr182Pro). This variant is present in population databases (rs751427686, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of SGCB-related conditions (PMID: 33250842, 35416532; Invitae). ClinVar contains an entry for this variant (Variation ID: 466604). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SGCB protein function. This variant disrupts the p.Thr182 amino acid residue in SGCB. Other variant(s) that disrupt this residue have been observed in individuals with SGCB-related conditions (PMID: 9032047), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000544134 SCV002019196 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-10-02 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000544134 SCV002073027 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2E criteria provided, single submitter clinical testing The missense variant p.T182P in SGCB (NM_000232.4) has been previously submitted in ClinVar as variant of uncertain significance.The variant has not been previously reported in literature in affected individuals. A different missense substitution at this codon (p.Thr182Ala) has been reported in the compound heterozygous state with a pathogenic variant in an individual affected with SGCB-related disease (Duggan DJ et al). The p.T182P variant is observed in 3/30,612 (0.0098%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.T182P missense variant is predicted to be damaging by both SIFT and PolyPhen2. The threonine residue at codon 182 of SGCB is conserved in all mammalian species. The nucleotide c.544 in SGCB is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Baylor Genetics RCV000544134 SCV004200998 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-05-23 criteria provided, single submitter clinical testing
Natera, Inc. RCV000544134 SCV002082980 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2E 2019-11-11 no assertion criteria provided clinical testing

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