ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.523A>G (p.Met175Val)

dbSNP: rs876661083
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217754 SCV000279481 uncertain significance not provided 2023-02-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Gordon2000[Book])
Invitae RCV000538286 SCV000626251 uncertain significance Fanconi anemia 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 175 of the FANCC protein (p.Met175Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC 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: 234556). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV000560923 SCV000673347 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-03 criteria provided, single submitter clinical testing The p.M175V variant (also known as c.523A>G), located in coding exon 6 of the FANCC gene, results from an A to G substitution at nucleotide position 523. The methionine at codon 175 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well 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. RCV000538286 SCV002081255 uncertain significance Fanconi anemia 2020-12-02 no assertion criteria provided clinical testing

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