ClinVar Miner

Submissions for variant NM_000023.4(SGCA):c.409G>A (p.Glu137Lys)

gnomAD frequency: 0.00001  dbSNP: rs372210292
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725776 SCV000339307 pathogenic not provided 2017-07-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000341255 SCV000649771 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 137 of the SGCA protein (p.Glu137Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with limb-girdle muscular dystrophy (LGMD) (PMID: 9192266, 12075495, 19798725, 25214167, 26916285). ClinVar contains an entry for this variant (Variation ID: 286049). 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 expected to disrupt SGCA protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SGCA function (PMID: 22095924). This variant disrupts the p.Glu137 amino acid residue in SGCA. Other variant(s) that disrupt this residue have been observed in individuals with SGCA-related conditions (PMID: 28403181), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000341255 SCV001367738 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP3. This variant was detected in homozygous state.
Revvity Omics, Revvity RCV000341255 SCV003825579 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2023-05-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000341255 SCV003931668 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2023-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000725776 SCV004168957 pathogenic not provided 2023-05-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 34426522, 31589614, 22095924, 9192266, 30703231, 21031578, 30764848, 16778590, 31069529, 12075495, 18285821, 25214167, 31980526, 19798725, 26916285, 24077912, 30107846)
Baylor Genetics RCV000341255 SCV004203165 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2024-03-27 criteria provided, single submitter clinical testing
Counsyl RCV000341255 SCV000789139 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2017-01-10 no assertion criteria provided clinical testing
Natera, Inc. RCV000341255 SCV001453379 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.