ClinVar Miner

Submissions for variant NM_000143.4(FH):c.1199A>G (p.Asn400Ser)

gnomAD frequency: 0.00001  dbSNP: rs764430466
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
Ambry Genetics RCV000568126 SCV000673391 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-04 criteria provided, single submitter clinical testing The p.N400S variant (also known as c.1199A>G), located in coding exon 8 of the FH gene, results from an A to G substitution at nucleotide position 1199. The asparagine at codon 400 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002526908 SCV001395452 uncertain significance not provided 2022-11-01 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 400 of the FH protein (p.Asn400Ser). This variant is present in population databases (rs764430466, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 485569). 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 serine 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.
Breakthrough Genomics, Breakthrough Genomics RCV002526908 SCV005186394 uncertain significance not provided criteria provided, single submitter not provided
Natera, Inc. RCV001223310 SCV002085302 uncertain significance Fumarase deficiency 2019-10-28 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.