ClinVar Miner

Submissions for variant NM_005271.5(GLUD1):c.965G>A (p.Arg322His)

dbSNP: rs121909737
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000017509 SCV000595006 pathogenic Hyperinsulinism-hyperammonemia syndrome 2017-03-27 criteria provided, single submitter clinical testing
Invitae RCV000017509 SCV000933885 pathogenic Hyperinsulinism-hyperammonemia syndrome 2022-12-16 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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 not expected to disrupt GLUD1 protein function. ClinVar contains an entry for this variant (Variation ID: 16129). This variant is also known as R269H. This missense change has been observed in individual(s) with hyperinsulinism hyperammonemia syndrome (PMID: 11214910, 27188453, 30306091). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 322 of the GLUD1 protein (p.Arg322His).
CeGaT Center for Human Genetics Tuebingen RCV001091338 SCV001247306 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000017509 SCV003936070 likely pathogenic Hyperinsulinism-hyperammonemia syndrome 2023-06-23 criteria provided, single submitter clinical testing A heterozygous variation in exon 7 of the GLUD1 gene that results in the amino acid substitution of Histidine for arginine at codon 322 was detected. The observed variant c.965G>A (p.Arg322His) has not been reported in the 1000 genomes databases. The in silico prediction of the variant are possibly damaging by LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as likely pathogenic.
OMIM RCV000017509 SCV000037781 pathogenic Hyperinsulinism-hyperammonemia syndrome 2001-01-01 no assertion criteria provided literature only

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