ClinVar Miner

Submissions for variant NM_001164277.1(SLC37A4):c.377G>A (p.Arg126Gln) (rs78735156)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498803 SCV000589428 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing The R126Q variant in the SLC37A4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R126Q variant was not observed in the homozygous state or at any significant frequency in approximately 6000 individuals ofEuropean and African American ancestry by the NHLBI Exome Sequencing Project. The R126Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R126Q as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV001102583 SCV001259268 uncertain significance Glycogen storage disease, type I 2018-03-30 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.
Invitae RCV001240285 SCV001413216 uncertain significance Glucose-6-phosphate transport defect 2019-09-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 126 of the SLC37A4 protein (p.Arg126Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs78735156, ExAC 0.09%). This variant has not been reported in the literature in individuals with SLC37A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 431869). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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