ClinVar Miner

Submissions for variant NM_014956.5(CEP164):c.2662C>G (p.Leu888Val) (rs142044303)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484217 SCV000569997 uncertain significance not provided 2016-04-15 criteria provided, single submitter clinical testing The L888V variant in the CEP164 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L888V variant was not observed with a significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L888V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L888V as a variant of uncertain significance.
Invitae RCV001071865 SCV001237195 uncertain significance Nephronophthisis 15 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 888 of the CEP164 protein (p.Leu888Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs142044303, ExAC 0.2%). This variant has not been reported in the literature in individuals with CEP164-related conditions. ClinVar contains an entry for this variant (Variation ID: 420952). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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