ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.998C>T (p.Ala333Val)

dbSNP: rs759611407
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001037060 SCV001200455 uncertain significance Cowden syndrome 2023-08-19 criteria provided, single submitter clinical testing 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. 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 PIK3CA protein function. ClinVar contains an entry for this variant (Variation ID: 836035). This variant has not been reported in the literature in individuals affected with PIK3CA-related conditions. This variant is present in population databases (rs759611407, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 333 of the PIK3CA protein (p.Ala333Val).
Ambry Genetics RCV002379485 SCV002694054 uncertain significance Inborn genetic diseases 2024-02-01 criteria provided, single submitter clinical testing The p.A333V variant (also known as c.998C>T), located in coding exon 4 of the PIK3CA gene, results from a C to T substitution at nucleotide position 998. The alanine at codon 333 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004528345 SCV004104642 uncertain significance PIK3CA-related disorder 2022-12-21 criteria provided, single submitter clinical testing The PIK3CA c.998C>T variant is predicted to result in the amino acid substitution p.Ala333Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-178921516-C-T) and interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/836035/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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