ClinVar Miner

Submissions for variant NM_004104.5(FASN):c.2593G>A (p.Asp865Asn) (rs199546508)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000554529 SCV000634952 uncertain significance Epileptic encephalopathy 2018-09-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 865 of the FASN protein (p.Asp865Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant also falls at the last nucleotide of exon 16 of the FASN coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs199546508, ExAC 0.05%) but has not been reported in the literature in individuals with a FASN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098) but according to multiple splice site algorithms this particular variant is not predicted to significantly affect splicing. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.

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