ClinVar Miner

Submissions for variant NM_001291303.3(FAT4):c.4543G>A (p.Val1515Met)

gnomAD frequency: 0.00006  dbSNP: rs773912269
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001171741 SCV001334579 uncertain significance not provided 2020-02-01 criteria provided, single submitter clinical testing
Invitae RCV001171741 SCV002170278 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1515 of the FAT4 protein (p.Val1515Met). This variant is present in population databases (rs773912269, gnomAD 0.01%). 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: 916196). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Clinical Genomics Laboratory, Washington University in St. Louis RCV003458223 SCV004176984 uncertain significance Hennekam lymphangiectasia-lymphedema syndrome 2 2023-09-01 criteria provided, single submitter clinical testing The FAT4 c.4543G>A (p.Val1515Met) variant was identified at a near heterozygous allelic fraction. This variant, to our knowledge, has not been reported in the medical literature. This variant has been reported in the ClinVar database as a variant of uncertain significance by two submitters (ClinVar ID: 916196) and has been reported in one case in the cancer database COSMIC (Genomic Mutation ID : COSV67902393). This variant is only observed on 8/152222 alleles in the general population (gnomAD v.3.1.2), indicating it is not a common variant. Computational predictors are conflicting as to the impact of this variant on the 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.

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