ClinVar Miner

Submissions for variant NM_022725.3(FANCF):c.385C>G (p.Leu129Val) (rs61753271)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000764968 SCV000370172 uncertain significance Fanconi anemia, complementation group F 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000421185 SCV000511291 uncertain significance not provided 2017-01-25 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
GeneDx RCV000421185 SCV000572880 uncertain significance not provided 2017-02-09 criteria provided, single submitter clinical testing The L129V variant in the FANCF gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The L129V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L129V variant is a conservative amino acid substitution, which occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret L129V as a variant of uncertain significance.
Invitae RCV000395772 SCV000626388 uncertain significance Fanconi anemia 2019-10-24 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 129 of the FANCF protein (p.Leu129Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs61753271, ExAC 0.1%) but has not been reported in the literature in individuals with a FANCF-related disease. ClinVar contains an entry for this variant (Variation ID: 134348). 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 is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000764968 SCV000896145 uncertain significance Fanconi anemia, complementation group F 2018-10-31 criteria provided, single submitter clinical testing
ITMI RCV000121022 SCV000085190 not provided not specified 2013-09-19 no assertion provided reference population

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