ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1397T>C (p.Val466Ala)

dbSNP: rs1473423234
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001777098 SCV002012719 uncertain significance not provided 2020-10-05 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001868821 SCV002305060 uncertain significance Birt-Hogg-Dube syndrome 2022-03-14 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 466 of the FLCN protein (p.Val466Ala). This variant is not present in population databases (gnomAD no frequency). 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1321119). This variant has not been reported in the literature in individuals affected with FLCN-related conditions.
Ambry Genetics RCV002388664 SCV002697139 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-15 criteria provided, single submitter clinical testing The p.V466A variant (also known as c.1397T>C), located in coding exon 9 of the FLCN gene, results from a T to C substitution at nucleotide position 1397. The valine at codon 466 is replaced by alanine, an amino acid with similar properties. This alteration has been identified in an individual with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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