ClinVar Miner

Submissions for variant NM_000925.4(PDHB):c.937C>G (p.Pro313Ala)

gnomAD frequency: 0.00006  dbSNP: rs201105914
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199882 SCV000252052 uncertain significance not provided 2013-11-11 criteria provided, single submitter clinical testing p.Pro313Ala (CCT>GCT): c.937 C>G in exon 10 of the PDHB gene (NM_000925.3). The P313A missense substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is semi-conservative in that both Proline and Alanine are uncharged, non-polar amino acids, but the loss of Proline with its unique ring structure could affect the secondary structure of the PDHB protein. This change occurs at a highly conserved position in the PDHB protein, and a missense mutation at a nearby position (D319V) has been reported in association with pyruvate dehydrogenase deficiency. In-silico analyses are inconsistent in their predictions of whether or not P313A is damaging to the PDHB protein. Therefore, based on the currently available information, it is unclear whether P313A is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).
Illumina Laboratory Services, Illumina RCV001144885 SCV001305504 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 RCV001144885 SCV002261268 likely benign Pyruvate dehydrogenase E1-beta deficiency 2024-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV004658985 SCV005151756 uncertain significance Inborn genetic diseases 2024-06-10 criteria provided, single submitter clinical testing The c.937C>G (p.P313A) alteration is located in exon 10 (coding exon 10) of the PDHB gene. This alteration results from a C to G substitution at nucleotide position 937, causing the proline (P) at amino acid position 313 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001275344 SCV001460438 uncertain significance Pyruvate dehydrogenase complex deficiency 2020-09-16 no assertion criteria provided clinical testing

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