ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1285C>A (p.His429Asn)

dbSNP: rs375082054
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000817804 SCV000958387 uncertain significance Birt-Hogg-Dube syndrome 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 429 of the FLCN protein (p.His429Asn). This variant is present in population databases (rs375082054, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 660582). 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 with a negative predictive value of 80%. 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.
Ambry Genetics RCV001010754 SCV001170994 likely benign Hereditary cancer-predisposing syndrome 2022-11-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics RCV000817804 SCV004199775 uncertain significance Birt-Hogg-Dube syndrome 2023-10-24 criteria provided, single submitter clinical testing

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