ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.620A>T (p.His207Leu) (rs202038890)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469377 SCV000549947 uncertain significance Fanconi anemia 2018-08-22 criteria provided, single submitter clinical testing This sequence change replaces histidine with leucine at codon 207 of the FANCC protein (p.His207Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is present in population databases (rs202038890, ExAC 0.007%). This variant has been reported in individuals affected with breast cancer (PMID: 23028338) and in an individual affected with serous cystadenoma (PMID: 28767289). ClinVar contains an entry for this variant (Variation ID: 409651). 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: "Benign"; 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 RCV000480838 SCV000564975 uncertain significance not provided 2018-02-19 criteria provided, single submitter clinical testing This variant is denoted FANCC c.620A>T at the cDNA level, p.His207Leu (H207L) at the protein level, and results in the change of a Histidine to a Leucine (CAT>CTT). This variant has been observed in two individuals from familial breast cancer kindreds (Thompson 2012). FANCC His207Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the Hsp70 and GRP94 binding domains (Gordon & Buchwald 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available information, it is unclear whether FANCC His207Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000766067 SCV000897538 uncertain significance Fanconi anemia, complementation group C 2018-10-31 criteria provided, single submitter clinical testing

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