ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1622C>T (p.Pro541Leu)

gnomAD frequency: 0.00001  dbSNP: rs1554827120
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567655 SCV000673345 likely benign Hereditary cancer-predisposing syndrome 2024-03-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000630828 SCV000751796 uncertain significance Fanconi anemia 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 541 of the FANCC protein (p.Pro541Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV002293461 SCV002586867 uncertain significance not provided 2022-04-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV000630828 SCV002081123 uncertain significance Fanconi anemia 2020-02-21 no assertion criteria provided clinical testing

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