ClinVar Miner

Submissions for variant NM_177550.5(SLC13A5):c.644C>T (p.Ala215Val)

dbSNP: rs777563695
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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 RCV001213700 SCV001385346 uncertain significance Developmental and epileptic encephalopathy, 25 2023-07-17 criteria provided, single submitter clinical testing 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC13A5 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 943501). This missense change has been observed in individual(s) with clinical features of SLC13A5-related conditions (PMID: 32551328). This variant is present in population databases (rs777563695, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 215 of the SLC13A5 protein (p.Ala215Val).
GeneDx RCV001552190 SCV001772838 uncertain significance not provided 2019-06-29 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32551328)
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001213700 SCV001999888 uncertain significance Developmental and epileptic encephalopathy, 25 2021-11-02 criteria provided, single submitter curation The p.Ala215Val variant in SLC13A5 has been reported in 2 individuals with developmental and epileptic encephalopathy (PMID: 32551328) and has been identified in 0.003% (1/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs777563695). 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. Of the 2 affected individuals, 2 of those were homozygotes which increases the likelihood that the p.Ala215Val variant is pathogenic (PMID: 32551328). This variant has also been reported in ClinVar (Variation ID#: 943501) and has been interpreted as VUS by Invitae. 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.Ala215Val variant is uncertain. ACMG/AMP Criteria applied: PM3, PM2_supporting (Richards 2015).
Genome-Nilou Lab RCV001213700 SCV002055670 uncertain significance Developmental and epileptic encephalopathy, 25 2021-07-15 criteria provided, single submitter clinical testing

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