ClinVar Miner

Submissions for variant NM_177550.5(SLC13A5):c.317A>G (p.His106Arg)

gnomAD frequency: 0.00001  dbSNP: rs762062274
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001242699 SCV001415802 uncertain significance Developmental and epileptic encephalopathy, 25 2020-04-08 criteria provided, single submitter clinical testing 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. 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"). This variant has not been reported in the literature in individuals with SLC13A5-related conditions. This variant is present in population databases (rs762062274, ExAC 0.002%). This sequence change replaces histidine with arginine at codon 106 of the SLC13A5 protein (p.His106Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine.
CeGaT Center for Human Genetics Tuebingen RCV001311106 SCV001501151 uncertain significance not provided 2020-08-01 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001242699 SCV001999891 uncertain significance Developmental and epileptic encephalopathy, 25 2021-11-02 criteria provided, single submitter curation The p.His106Arg variant in SLC13A5 has been reported in 2 compound heterozygous individuals with developmental and epileptic encephalopathy (TESS cohort). In addition this variant segregated with disease in 1 affected relative from 1 family (TESS cohort), and has been identified in 0.003% (3/113138) of European (Non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs762062274). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 967719) and has been interpreted as VUS by Invitae and CeGaT Praxis fuer Humangenetik Tuebingen. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.His106Arg variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PM3_supporting (Richards 2015).
Genome-Nilou Lab RCV001242699 SCV002055680 uncertain significance Developmental and epileptic encephalopathy, 25 2021-07-15 criteria provided, single submitter clinical testing

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