ClinVar Miner

Submissions for variant NM_000232.5(SGCB):c.265G>A (p.Val89Met)

gnomAD frequency: 0.00001  dbSNP: rs762652676
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666951 SCV000791328 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2E 2017-05-10 criteria provided, single submitter clinical testing
Invitae RCV000666951 SCV001592853 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 89 of the SGCB protein (p.Val89Met). This variant is present in population databases (rs762652676, gnomAD 0.003%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 15938573). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 551805). 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%. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222588 SCV002500418 pathogenic Autosomal recessive limb-girdle muscular dystrophy 2022-03-16 criteria provided, single submitter clinical testing Variant summary: SGCB c.265G>A (p.Val89Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251442 control chromosomes (gnomAD). c.265G>A has been reported in the literature in multiple homozygous individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (e.g. Tasca_2018, Diniz_2017, Yis_2018, Feng_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic or as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic.
Revvity Omics, Revvity RCV000666951 SCV003808149 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-09-20 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000666951 SCV004171903 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E criteria provided, single submitter clinical testing

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