ClinVar Miner

Submissions for variant NM_000925.4(PDHB):c.448G>T (p.Ala150Ser)

gnomAD frequency: 0.00005  dbSNP: rs139242990
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000537624 SCV000445823 uncertain significance Pyruvate dehydrogenase E1-beta deficiency 2018-01-13 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000537624 SCV000651270 uncertain significance Pyruvate dehydrogenase E1-beta deficiency 2021-08-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 150 of the PDHB protein (p.Ala150Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs139242990, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with PDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 346409). 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: "Benign"; Align-GVGD: "Class C0"). 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.
GeneDx RCV004725181 SCV005334505 uncertain significance not provided 2023-10-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Natera, Inc. RCV001280188 SCV001467348 uncertain significance Pyruvate dehydrogenase complex deficiency 2020-09-20 no assertion criteria provided clinical testing

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