ClinVar Miner

Submissions for variant NM_002336.3(LRP6):c.2599A>G (p.Thr867Ala)

gnomAD frequency: 0.00014  dbSNP: rs141458215
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003558846 SCV004286020 uncertain significance not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 867 of the LRP6 protein (p.Thr867Ala). This variant is present in population databases (rs141458215, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with LRP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1255574). 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) performed at Invitae indicates that this missense variant is not expected to disrupt LRP6 protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LRP6 function (PMID: 26901136). 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.
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center RCV001844903 SCV001877037 uncertain significance Autosomal dominant polycystic liver disease 2021-09-01 no assertion criteria provided research

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