Submissions for variant NM_000136.3(FANCC):c.595del (p.Leu199fs)

dbSNP: rs1057519366

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483255	SCV000572484	likely pathogenic	not provided	2016-12-15	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in FANCC is denoted c.595delC at the cDNA level and p.Leu199TrpfsX25 (L199WfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is ACCCC[delC]TGGT. The deletion causes a frameshift which changes a Leucine to a Tryptophan at codon 199, and creates a premature stop codon at position 25 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Ambry Genetics	RCV002356785	SCV002658440	pathogenic	Hereditary cancer-predisposing syndrome	2022-02-08	criteria provided, single submitter	clinical testing	The c.595delC pathogenic mutation, located in coding exon 6 of the FANCC gene, results from a deletion of one nucleotide at nucleotide position 595, causing a translational frameshift with a predicted alternate stop codon (p.L199Wfs*25). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV002525919	SCV003508045	pathogenic	Fanconi anemia	2021-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu199Trpfs*25) in the FANCC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 422895). For these reasons, this variant has been classified as Pathogenic.