ClinVar Miner

Submissions for variant NM_001164277.2(SLC37A4):c.497G>A (p.Arg166His)

gnomAD frequency: 0.00076  dbSNP: rs186476316
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199219 SCV000252289 likely pathogenic not provided 2015-07-28 criteria provided, single submitter clinical testing p.Arg166His (CGC>CAC): c.497 G>A in exon 5 of the SLC37A4 gene (NM_001164277.1) The R166H variant in the SLC37A4 gene is likely pathogenic. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. Mutations in the SLC37A4 gene are associated with the autosomal recessive disorders glycogen storage disease Ib and Ic The R166H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is highly conserved across species. A non-conservative missense change at the same position (R166L) has been reported previously in association with glycogen storage disease Ib (Chen et al., 2008). In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (A156V, C176R) have also been reported in association with glycogen storage disease Ib, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in LAPDH-MITOP,MITONUC-MITOP panel(s).
Eurofins Ntd Llc (ga) RCV000199219 SCV000700710 uncertain significance not provided 2014-07-10 criteria provided, single submitter clinical testing
Invitae RCV001084902 SCV000755873 benign Glucose-6-phosphate transport defect 2024-01-29 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001027800 SCV001190413 uncertain significance Phosphate transport defect; Glucose-6-phosphate transport defect 2019-06-20 criteria provided, single submitter clinical testing SLC37A4 NM_001164277.1 exon 5 p.Arg166His (c.497G>A): This variant has not been reported in the literature but is present in 0.3% (73/23994) of African alleles in the Genome Aggregation Database, including one homozygote (https://gnomad.broadinstitute.org/variant/11-118898467-C-T). This variant is present in ClinVar (Variation ID:215178). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, another variant at this residue (p.Arg166Leu) has been reported in association with disease (Glycogen storage disease 1B) (Kojima 2004 PMID:15059622, Chen 2008 PMID:18835800). In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224223 SCV003920484 uncertain significance Phosphate transport defect; Glucose-6-phosphate transport defect; Congenital disorder of glycosylation, type IIw 2021-03-30 criteria provided, single submitter clinical testing SLC37A4 NM_001164277.1 exon 5 p.Arg166His (c.497G>A): This variant has not been reported in the literature but is present in 0.3% (73/23994) of African alleles in the Genome Aggregation Database, including one homozygote (https://gnomad.broadinstitute.org/variant/11-118898467-C-T). This variant is present in ClinVar (Variation ID:215178). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, another variant at this residue (p.Arg166Leu) has been reported in association with disease (Glycogen storage disease 1B) (Kojima 2004 PMID:15059622, Chen 2008 PMID:18835800). In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Natera, Inc. RCV001084902 SCV001466217 benign Glucose-6-phosphate transport defect 2020-10-21 no assertion criteria provided clinical testing

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