ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1081C>T (p.Arg361Trp) (rs768508859)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206395 SCV000259606 uncertain significance Fanconi anemia 2015-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 361 of the FANCC protein (p.Arg361Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases and has not been published in the literature. 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, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000479585 SCV000571736 uncertain significance not provided 2017-04-17 criteria provided, single submitter clinical testing This variant is denoted FANCC c.1081C>T at the cDNA level, p.Arg361Trp (R361W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Arg361Trp was not observed in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Arginine and Tryptophan differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. FANCC Arg361Trp occurs at a position that is not conserved and is located in the Hsp70 binding domain (Gordon 2000). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether FANCC Arg361Trp is pathogenic or benign. We consider it to be a variant of uncertain significance.

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