ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.4892C>T (p.Ser1631Leu) (rs748759724)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434578 SCV000532537 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing The S1631L variant in the C5orf42 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S1631L variant was not observed 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 S1631L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S1631L as a variant of uncertain significance.
Invitae RCV000646705 SCV000768484 uncertain significance Orofaciodigital syndrome 6; Joubert syndrome 17 2017-08-11 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 1631 of the C5orf42 protein (p.Ser1631Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs748759724, ExAC 0.02%). This variant has not been reported in the literature in individuals with C5orf42-related disease. ClinVar contains an entry for this variant (Variation ID: 389868). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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