ClinVar Miner

Submissions for variant NM_001291303.3(FAT4):c.1378A>G (p.Ser460Gly)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002638490 SCV003521171 uncertain significance not provided 2022-07-30 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 460 of the FAT4 protein (p.Ser460Gly). This variant is present in population databases (rs772780567, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with FAT4-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002644275 SCV003698411 uncertain significance Inborn genetic diseases 2022-04-07 criteria provided, single submitter clinical testing The c.1378A>G (p.S460G) alteration is located in exon 1 (coding exon 1) of the FAT4 gene. This alteration results from a A to G substitution at nucleotide position 1378, causing the serine (S) at amino acid position 460 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV002638490 SCV005334295 uncertain significance not provided 2023-08-11 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
Fulgent Genetics, Fulgent Genetics RCV005028308 SCV005660414 uncertain significance Van Maldergem syndrome 2; Hennekam lymphangiectasia-lymphedema syndrome 2 2024-05-31 criteria provided, single submitter clinical testing

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