ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1366A>G (p.Met456Val)

gnomAD frequency: 0.00001  dbSNP: rs1554828443
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000554186 SCV000626238 uncertain significance Fanconi anemia 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 456 of the FANCC protein (p.Met456Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 23028338). ClinVar contains an entry for this variant (Variation ID: 456157). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCC protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV001011062 SCV001171341 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-31 criteria provided, single submitter clinical testing The p.M456V variant (also known as c.1366A>G), located in coding exon 13 of the FANCC gene, results from an A to G substitution at nucleotide position 1366. The methionine at codon 456 is replaced by valine, an amino acid with highly similar properties. This variant was identified in 1 of 1441 individuals from high risk breast cancer families and in 0 of 464 healthy controls (Thompson ER et al. PLoS Genet. 2012 Sep;8:e1002894).This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001273980 SCV001457641 uncertain significance Fanconi anemia complementation group C 2020-09-16 no assertion criteria provided clinical testing

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