ClinVar Miner

Submissions for variant NM_001040716.2(PC):c.1771G>A (p.Ala591Thr)

gnomAD frequency: 0.00011  dbSNP: rs139795235
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001239246 SCV001412103 uncertain significance Pyruvate carboxylase deficiency 2022-10-25 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 591 of the PC protein (p.Ala591Thr). This variant is present in population databases (rs139795235, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PC-related conditions. ClinVar contains an entry for this variant (Variation ID: 964921). 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 PC 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.
GeneDx RCV001760259 SCV001991892 uncertain significance not provided 2021-04-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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