ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro) (rs104886458)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000058925 SCV000512973 pathogenic not provided 2018-06-27 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1661T>C at the cDNA level, p.Leu554Pro (L554P) at the proteinlevel, and results in the change of a Leucine to a Proline (CTG>CCG) in exon 15. This variant has observed in atleast two individuals with Fanconi Anemia (Verlander 1994). This variant was also identified in an individual with twoprimary breast cancers and a family history of breast cancer (Thompson 2012). Functional studies of this pathogenic variantresults in decreased capacity to tolerate mitomycin C and the inability to bind to FANCA, FANCE, and cdc2 (Gavish1993, Youssoufian 1996, Kupfer 1997a, Kupfer 1997b, Gordon 2003). FANCC Leu554Pro was not observed at asignificant allele frequency in the NHLBI Exome Sequencing Project. Since Leucine and Proline differ in someproperties, this is considered a semi-conservative amino acid substitution. FANCC Leu554Pro alters a position that ishighly conserved across species and is located in the cdc2 binding domain (Gordon 2000). In silico analyses predictthat this variant is probably damaging to protein structure and function. Based on the current evidence, we considerthis to be a pathogenic variant.
GeneReviews RCV000012823 SCV000057806 pathogenic Fanconi anemia, complementation group C 2016-09-22 no assertion criteria provided literature only
OMIM RCV000012823 SCV000033063 pathogenic Fanconi anemia, complementation group C 1996-02-15 no assertion criteria provided literature only
SNPedia RCV000058925 SCV000090446 not provided not provided no assertion provided not provided

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