Submissions for variant NM_000337.6(SGCD):c.92G>A (p.Arg31Gln)

gnomAD frequency: 0.00016  dbSNP: rs200476861

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723938	SCV000228858	uncertain significance	not provided	2018-08-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000723938	SCV000236390	uncertain significance	not provided	2024-11-26	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in an individual who died of sudden cardiac death (PMID: 33919104); This variant is associated with the following publications: (PMID: 30564623, Pourebrahim2021[article], 33919104)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000212998	SCV000272433	uncertain significance	not specified	2018-10-11	criteria provided, single submitter	clinical testing	The p.Arg31Gln variant in SGCD has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 0.03% (39/126184) of European chr omosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein , though this information is not predictive enough to determine pathogenicity. I n summary, the clinical significance of the p.Arg31Gln variant is uncertain. ACM G/AMP Criteria applied: BS1_Supporting, PP3.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554394	SCV000638183	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2F	2022-09-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 31 of the SGCD protein (p.Arg31Gln). This variant is present in population databases (rs200476861, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SGCD-related conditions. ClinVar contains an entry for this variant (Variation ID: 196255). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852562	SCV000995262	uncertain significance	Cardiomyopathy	2019-02-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001156233	SCV001317720	uncertain significance	Qualitative or quantitative defects of delta-sarcoglycan	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000723938	SCV002009253	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000723938	SCV002542148	uncertain significance	not provided	2021-12-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002485153	SCV002785275	uncertain significance	Dilated cardiomyopathy 1L; Autosomal recessive limb-girdle muscular dystrophy type 2F	2021-08-03	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000723938	SCV003819896	uncertain significance	not provided	2021-12-27	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000554394	SCV003931771	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2F	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003233484	SCV003931772	uncertain significance	Dilated cardiomyopathy 1L	2023-02-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000212998	SCV004241708	likely benign	not specified	2023-12-04	criteria provided, single submitter	clinical testing	Variant summary: SGCD c.92G>A (p.Arg31Gln) 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 0.00017 in 247440 control chromosomes, predominantly at a frequency of 0.00034 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 13.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in SGCD causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.92G>A has been reported in the literature in individuals affected with dilated cardiomyopathy or sudden cardiac death with left ventricular hypertrophy without evidence of cosegregation with disease (Pourebrahim_2021, Iglesias_2021). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33919104, 34790974). 11 submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000723938	SCV001740368	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000723938	SCV001927591	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000723938	SCV001965973	uncertain significance	not provided		no assertion criteria provided	clinical testing