ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1589T>C (p.Leu530Ser) (rs766809608)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198094 SCV000254255 uncertain significance Fanconi anemia 2018-08-06 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 530 of the FANCC protein (p.Leu530Ser). The leucine residue is moderately conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs766809608, ExAC 0.009%). This variant has not been reported in the literature in individuals with a FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 216284). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on FANCC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000221697 SCV000279385 uncertain significance not provided 2018-01-03 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1589T>C at the cDNA level, p.Leu530Ser (L530S) at the protein level, and results in the change of a Leucine to a Serine (TTG>TCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Leu530Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the cdc2 binding region (Gordon 2000). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FANCC Leu530Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000561073 SCV000673321 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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