ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1262G>A (p.Ser421Asn)

gnomAD frequency: 0.00001  dbSNP: rs368175757
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001045667 SCV001209533 uncertain significance Birt-Hogg-Dube syndrome 2023-03-22 criteria provided, single submitter clinical testing 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. 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 FLCN protein function. ClinVar contains an entry for this variant (Variation ID: 843120). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 421 of the FLCN protein (p.Ser421Asn).
Ambry Genetics RCV002445245 SCV002680602 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-16 criteria provided, single submitter clinical testing The p.S421N variant (also known as c.1262G>A), located in coding exon 8 of the FLCN gene, results from a G to A substitution at nucleotide position 1262. The serine at codon 421 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV001045667 SCV004195333 uncertain significance Birt-Hogg-Dube syndrome 2023-08-10 criteria provided, single submitter clinical testing

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