ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.16G>A (p.Ala6Thr)

gnomAD frequency: 0.00006  dbSNP: rs768396832
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000990497 SCV001141501 likely benign Pyruvate dehydrogenase E1-alpha deficiency 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000990497 SCV003258678 uncertain significance Pyruvate dehydrogenase E1-alpha deficiency 2024-08-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 6 of the PDHA1 protein (p.Ala6Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PDHA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 803731). 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 PDHA1 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.
Ambry Genetics RCV004030119 SCV005003719 likely benign Inborn genetic diseases 2023-12-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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