ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.956C>T (p.Thr319Met)

gnomAD frequency: 0.00001  dbSNP: rs745910444
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000824523 SCV000965423 uncertain significance Fanconi anemia 2022-02-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 319 of the FANCC protein (p.Thr319Met). This variant is present in population databases (rs745910444, gnomAD 0.007%). 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: 666102). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001759625 SCV001985253 uncertain significance not provided 2023-09-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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], 27397505)
Ambry Genetics RCV002372363 SCV002690781 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The p.T319M variant (also known as c.956C>T), located in coding exon 9 of the FANCC gene, results from a C to T substitution at nucleotide position 956. The threonine at codon 319 is replaced by methionine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, methionine is the reference amino acid in other 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. RCV001274467 SCV001458690 uncertain significance Fanconi anemia complementation group C 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.