ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1627_1628delinsAA (p.Ser543Lys) (rs864622417)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205177 SCV000260561 uncertain significance Fanconi anemia 2019-10-30 criteria provided, single submitter clinical testing This sequence change replaces serine with lysine at codon 543 of the FANCC protein (p.Ser543Lys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 220199). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly damaging"; 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 RCV000483541 SCV000572321 uncertain significance not specified 2016-11-18 criteria provided, single submitter clinical testing This in-frame deletion and insertion in FANCC is denoted c.1627_1628delTCinsAA at the cDNA level and p.Ser543Lys (S543K) at the protein level, and results in the change of a Serine to a Lysince (TCA>AAA). The normal sequence, with the bases that are deleted and inserted in braces, is TAGA[delTC][insAA]AGAA. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FANCC Ser543Lys occurs at a position that is not covered in the NLHBI Exome Sequencing Project. Since Serine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. FANCC Ser543Lys occurs in a region that is not conserved and is located in the cdc2 binding domain (Gordon & Buchwald 2000). In silico analyses predict that this variant is unlikely to alter protein structure or function. We consider it to be a variant of uncertain significance.

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