Submissions for variant NM_000136.3(FANCC):c.509A>G (p.Asn170Ser)

dbSNP: rs749322338

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000467727	SCV000549967	uncertain significance	Fanconi anemia	2025-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 170 of the FANCC protein (p.Asn170Ser). This variant is present in population databases (rs749322338, gnomAD 0.0009%). 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: 409660). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
GeneDx	RCV001560667	SCV001783124	uncertain significance	not provided	2024-02-28	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: 15695377)
Genome-Nilou Lab	RCV001276457	SCV001786855	uncertain significance	Fanconi anemia complementation group C	2021-07-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002339166	SCV002642455	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-30	criteria provided, single submitter	clinical testing	The p.N170S variant (also known as c.509A>G), located in coding exon 5 of the FANCC gene, results from an A to G substitution at nucleotide position 509. The asparagine at codon 170 is replaced by serine, 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001560667	SCV004218682	uncertain significance	not provided	2023-06-21	criteria provided, single submitter	clinical testing	This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/251178 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics	RCV001276457	SCV005677502	uncertain significance	Fanconi anemia complementation group C	2024-02-24	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001276457	SCV001462828	uncertain significance	Fanconi anemia complementation group C	2020-09-16	no assertion criteria provided	clinical testing