ClinVar Miner

Submissions for variant NM_004820.5(CYP7B1):c.1031A>C (p.Glu344Ala)

gnomAD frequency: 0.00001  dbSNP: rs1057518485
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412720 SCV000492164 uncertain significance not specified 2016-12-02 criteria provided, single submitter clinical testing The E344A variant in the CYP7B1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E344A 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 E344A 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 where amino acids with similar properties to Glutamic acid are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E344A as a variant of uncertain significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848734 SCV002104541 uncertain significance Hereditary spastic paraplegia 2016-12-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002521428 SCV003457492 uncertain significance Spastic paraplegia 2022-03-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 344 of the CYP7B1 protein (p.Glu344Ala). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CYP7B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 373563). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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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