ClinVar Miner

Submissions for variant NM_001291303.3(FAT4):c.7264A>T (p.Ser2422Cys)

gnomAD frequency: 0.00011  dbSNP: rs139924242
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
GeneDx RCV001763380 SCV001990799 uncertain significance not provided 2019-03-29 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001763380 SCV002204130 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2420 of the FAT4 protein (p.Ser2420Cys). This variant is present in population databases (rs139924242, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1308468). 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 FAT4 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.
Ambry Genetics RCV002538837 SCV003561781 uncertain significance Inborn genetic diseases 2021-12-03 criteria provided, single submitter clinical testing The c.7258A>T (p.S2420C) alteration is located in exon 8 (coding exon 8) of the FAT4 gene. This alteration results from a A to T substitution at nucleotide position 7258, causing the serine (S) at amino acid position 2420 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genomics Laboratory, Washington University in St. Louis RCV004558636 SCV005047148 uncertain significance Hennekam lymphangiectasia-lymphedema syndrome 2 2024-03-06 criteria provided, single submitter clinical testing A FAT4 c.7264A>T (p.Ser2422Cys) variant was identified at a heterozygous allelic fraction of 51%, a frequency which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline variant of uncertain significance by three submitters (ClinVar ID: 1308468). The FAT4 c.7264A>T (p.Ser2422Cys) variant is only observed on 30/1,608,816 alleles in the general population (gnomAD v.4.0.0), indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on FAT4 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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.