ClinVar Miner

Submissions for variant NM_000337.5(SGCD):c.92G>A (p.Arg31Gln) (rs200476861)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723938 SCV000228858 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing
GeneDx RCV000723938 SCV000236390 uncertain significance not provided 2018-09-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SGCD gene. The R31Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R31Q variant is observed in 39/126184 (0.03%) alleles from individuals of European background (Lek et al., 2016). The R31Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Laboratory for Molecular Medicine, Partners HealthCare 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 ( 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.
Invitae RCV000554394 SCV000638183 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2F 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 31 of the SGCD protein (p.Arg31Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200476861, ExAC 0.03%). This variant has not been reported in the literature in individuals with SGCD-related disease. ClinVar contains an entry for this variant (Variation ID: 196255). Algorithms developed to predict the effect of missense changes on protein structure and function 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, but this prediction has not been confirmed by published transcriptional studies. 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 Clinical Services Laboratory,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.

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