ClinVar Miner

Submissions for variant NM_024582.4(FAT4):c.8326A>G (p.Ile2776Val) (rs773858750)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492988 SCV000582850 uncertain significance not provided 2017-05-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the FAT4 gene. The c.8326 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.8326 A>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.8326 A>G creates a cryptic donor site upstream of the natural donor site of exon 9 and may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If c.8326 A>G does not alter splicing, it will result in the I2776V missense change. The I2776V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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