ClinVar Miner

Submissions for variant NM_000232.5(SGCB):c.271C>T (p.Arg91Cys)

gnomAD frequency: 0.00002  dbSNP: rs555514820
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596054 SCV000704557 likely pathogenic not provided 2018-09-14 criteria provided, single submitter clinical testing
Invitae RCV000813259 SCV000953611 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 91 of the SGCB protein (p.Arg91Cys). This variant is present in population databases (rs555514820, gnomAD 0.01%). This missense change has been observed in individuals with limb-girdle muscular dystrophy (PMID: 9565988, 17994539). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 499193). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect SGCB function (PMID: 22095924). This variant disrupts the p.Arg91 amino acid residue in SGCB. Other variant(s) that disrupt this residue have been observed in individuals with SGCB-related conditions (PMID: 8968749, 9631401), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001267014 SCV001445195 pathogenic Inborn genetic diseases 2018-02-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001779022 SCV002015169 pathogenic Autosomal recessive limb-girdle muscular dystrophy 2021-10-04 criteria provided, single submitter clinical testing Variant summary: SGCB c.271C>T (p.Arg91Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251452 control chromosomes. c.271C>T has been reported in the literature as a compound heterozygous or homozygous genotype in multiple individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (example, Duclos_1998, Guglieri_2008, Magri_2015). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function by confocal immunofluorescence analysis of non-permeabilized cells and classifies this variant as a class I - mutation that did not affect the membrane localization of Sarcoglycan B (Soheilli_2012). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Revvity Omics, Revvity RCV000813259 SCV002019198 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2022-12-16 criteria provided, single submitter clinical testing
Baylor Genetics RCV000813259 SCV004208736 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-10-06 criteria provided, single submitter clinical testing
Counsyl RCV000813259 SCV001132480 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2017-04-17 no assertion criteria provided clinical testing
Natera, Inc. RCV000813259 SCV001460964 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2020-09-16 no assertion criteria provided clinical testing

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